From San Andreas-

This is after doing a few missions (including a car race and a shootout) with Wu Zi Mu, who wears dark glasses.

Wu Zi Mu: I Have a confession to make... I... I'm blind.

CJ:... No shit!

Just the way he says it is hilarious.

Aha! video!
http://youtube.com/watch?v=vM_AAidZmyw

River City Ransom: "BARF!"

Wow, there's some pretty great stuff up here.

From Killer7:

Harman: Nothing has changed for 30 years. No matter how many times you try, the result will be the same.
Kun Lan: Ahh, yes. Like our chess games, you always seem to win.
Harman: Do you know why?
Kun Lan: You tell me.
Harman: Because you're a bad player.

Video: http://www.youtube.com/watch?v=D6JGA4xSudU

Halo 2. Final level where you get to play as Master Chief. Only one marine has survived to tag along with me, he has a plasma rifle, I have a carbine and a depleted energy sword. we both enter the bathisphere thingy, and after Cortana's lecture while in tranist, I look up at him. He's covered in blood, his health is low. After a moment of looking, he speaks.

"Have we tried -REASONING- with them...?"

Resident Evil 4:

Salazar: Well then Leon - I have sent my right hand to dispose of you.

Leon: Your right hand comes off?

Always cracks me up ;D

From Starcraft, and Starcraft: Brood War:

The classic Marine:
"We gotta move!"
"Are you gonna give me orders?"
"Oh my god! He's whacked!"
"I vote we frag this commander."
"How do I get out off this chicken **** outfit?!"

And the firebat...
"Is something burning?"
"Haha, that's what I thought."
"I love the smell of napalm."
"Nothing like a good smoke!"
"Are you trying to get invited to my barbecue?"
"Got any questions about propane?"
"Or, propane accessories?"

The SCV...
"Come again, Captain?"
"I'm not readin' you clearly."
"You ain't from around here, are you?"
"I can't believe they put me in one of these things!"
"And now I gotta put up with this too?"
"I told em I was claustrophobic, I gotta get outta here!"
"I'm locked in here tighter than a frog's butt in a watermelon seed fight."

We can go on....

"all your base are belong to us" :)

Bioshock

"she wont stay still! I want to make them beautiful, but they always turn out wrong! That one too fat; this one, too tall; this one, too symmetrical! And now... whats this guys? An intruder! HIS UGLY! UGLY! UGLLYYYYYYYY!"

http://youtube.com/watch?v=w_naGYiSJ6k

"What will you do?"
"Thought I'd shoot my way out, mix it up a bit."

- Cortana speaking to Master Chief

Not a huge fan of Halo, but I love some quick, smack in the face tongue in cheek humor like this.

"Major Tom, can you hear me?"

-Naked Snake speaking to Major Tom

"Deep into that darkness peering, long I stood there, wondering, fearing, doubting."
- Edward Roivas

No doubt dozens more I'm not thinking of right now, but those are some good ones that come to mind.

Planescape Torment, Monkey Island and Fallout have some great lines, but nog when taken out of context. Apart from the "farting to the south" line.

System Shock 2 has some chilling monologue, I don't think I'll ever forget:
Shodan: Look at you, hacker: a pathetic creature of meat and bone, panting and sweating as you run through my corridors. How can you challenge a perfect, immortal machine?

and:
The Many: What is a drop of rain, compared to the storm? What is a thought, compared to the mind? Our unity is full of wonder which your tiny individualism cannot even conceive.

"I love you, sarge!" - Starcraft.

"Somebody set us up the bomb"

Cuz we can close the thread after i post this, there is nothing who can beat that one! Not even a ninja bear with lazor claws!

Edit - Source : http://www.youtube.com/watch?v=qItugh-fFgg
I really dont know the name of the game :(

Some of Kazooie's lines from Banjo-Kazooie and its sequel were terrific...

When meeting space aliens:
Kazooie: "Are any of you guys named Elvis?"

Later, the alien says something like: "Now, we need to ask a favor of you."
Kazooie: "Let me guess. You need to phone home?"
Alien: "No, we have cell phones for that."

Shadow Warrior: "You tiny grasshopper!"
"You bad man! You should try harder get along."

I remembered another one.
"What happened to the cat?" from Half Life 2.

Mass Effect, when you first see the Thorian:

You: Thats......large.

I had to revive this thread, because nobody mentioned anything from the System Shock series!

SHODAN has one of the best quotes in videogames, ever:

"Look at you, Hacker. A pathetic creature of meat and bone, panting and sweating as you run through my corridors. How can you challenge a perfect, immortal machine?"

GLaDOS is funnier, but she can't even begin to touch SHODAN's goddess-complex:

"Are you afraid? What is it that you fear? The end of your trivial existence?"
"When the history of my glory is written, your species shall only be a footnote to my magnificence."
"You move like an insect. You think like an insect. You are an insect. There is another... who can serve my purpose. Take care not to fall too far out of my favour. Patience is not characteristic of a Goddess."

Pretty much all the dialogue in that game is brilliant. The Many have some great lines as well:

"Mistrust is the tyranny of the individual. Your own kind sees you as a threat. Why do you murder our unity? No matter, the line is drawn. You will cease to be. It is just a question of who will bring your end. Us? Or you?"

"Your time is running out. This place is a womb, where we grow our future. Your weapons fail, your ammunition runs low, and you've yet to see our most beautiful creation. All you have is your hatred, and your... individuality. Now don't you wish you joined us? Would you then feel so alone?"

I especially loved how you often got peeks of the last vestiges of normality through the corrupted monsters that populated the game - like the way the human/annelid hybrids apologized sometimes as they attacked you, or the robot butlers in the mall level would politely ask if they could help you with anything while they attacked.

"That was close! You were almost a Jill sandwich!"
-Barry (Resident Evil 1)

Notable due to the absolutely horrible voice acting that made me giggle like a woman when i first heard it.

Man, you guys already have a lot of great ones posted up here.

In the so-bad-it's-good department, I submit just about the entirety of Chrome. An example:

Bolt Logan (having just cleared an area in a vicious firefight): Alright, I've blown them all to hell!
Carrie (from the previous room, sounding absurdly peppy): O-kay!

PORTAL SONG

this was a triump, im making a not here: HUGE SUCCESS!
It's hard to overstate my satisfaction.
Aperture Science. We do what we must, because we can.
For the good of all of us, except the ones who are dead.
But theres no sense crying over mistake, you just keep on trying till you run out of cake.
And the science gets done and you make a neat gun for the people who are still alive.

Im not even angry, im being so sincere right now.
Even though you broke my heart and killed me.
And tore me pieces. And threw every piece into a fire.
As they burn it hurt because i was so happy for you.
Now these points of data make a beautiful line,
And were out of beta, were releasing on time.
So i never got burned in all the things we learned for the people who are still alive.

Go ahead and leave me, i think i prefer to stay inside.
Maybe you'll find someone else to help you.
Maybe black mesa. That was a joke. Haha. Fat chance.
Anyway this cake is great. It's so delicious and moist.
Look at me still talking when theres science to do,
when i look out there it makes me glad im not you.
Ive experiments to be run there is research to be done on the people who are still alive.

And believe i am still alive - im doing science and im still alive - i feel fantistic and im still alive - while your dieing ill still be alive - and when you dead ill stil be alive - still alive - still alive...

mrcheese:
"That was close! You were almost a Jill sandwich!"
-Barry (Resident Evil 1)

Notable due to the absolutely horrible voice acting that made me giggle like a woman when i first heard it.

Also a great, really poorly delivered line from RE: "What is it?"

No One Lives Forever

[from the mission "Rendezvous in Hamburg, Scene 2"]
Random thug 1: Our studies show that criminals drink three times as much alcohol as law abiding citizens.
Random thug 2: So beer turns people into criminals?
Thug 1: A correlation doesn't imply causality. Just because criminals drink a lot of beer doesn't mean that beer causes crime. It's possible that people with criminal tendencies enjoy beer because it helps to soothe their conscience. Or perhaps criminal behavior is caused in part by a genetic predisposition that also, coincidentally, makes criminals like the taste of beer more than the average person. Who knows?
Thug 2: You're very knowledgeable about these things.
Thug 1: Criminal sociology is a hobby of mine. I think it's important to understand not just the individual, psychological roots of one's behavior, but also the social circumstances that foster that behavior. Whether we like it or not, we are shaped by our environment.
Thug 2: Surely you're not suggesting that individuals aren't accountable for their actions.
Thug 1: Oh, no, of course not. Just because we are products of the societies we're born into doesn't absolve us of personal responsibility. Our religions and laws teach us what is right and what is wrong. Frequently, the right choice is the more difficult path to take. It requires sacrifice, self-discipline, patience ... virtues that many of us find somewhat lacking in our natures.
Thug 2: But what if you're born into a hedonistic culture?
Thug 1: Look across history. The reason hedonism is discouraged by most religions and governments is that it weakens a civilization. It breeds sloth, petulance, degeneracy, and selfishness. A divided nation is a fragile nation, waiting to be conquered. Unity is strength. Humans instinctively fashion order out of chaos. It is a natural, probably genetic impulse. Therefore, even an individual born into troubled times has the capacity, and even the duty, to behave in a manner that promotes unity, however difficult it may be.
Thug 2: Then what about us?
Thug 1: I can only speak for myself. I am a product of a broken household, which introduced a general lack of self confidence in me at a very early age. These feelings of inadequacy blossomed into anger as I matured that the rigors of adolescence, with the teasing and abuse and awkwardness we must all endure, only exacerbated. But even though I've identified the source of my problems, I'm still too childish and petty to become a responsible, mature citizen.
Thug 2: Well, admitting you have a problem is the first step, I suppose.
Thug 1: I like to think so.

Dead Rising-carlito"Aren't zombies great?"

Resident Evil 4

"What a ya' BUYIN?"
"What a ya' SELLIN?"
"Heh Heh Heh, Thank you!"
"Is that all, strange-ah?"
"Come back anytime!"
"I see you have an eye for things. Gun's not just about shootin'. It's about reloadin'. You'll know what I'm talkin' about."
- The Merchant

"Policia, you put your life on the line, no one really appreciates you enough for it. Being a hero isn't what it's cracked up to be anymore." - Luis

"Small world, eh? Well, I see that the President's equipped his daughter with...ballistics." - Luis

"I've been expecting you my brethrens." - Salazar
"No thanks, BRO!" - Leon

"Luis! LUUUUIIIIIIIIIIISSSS!!" - Leon

"Snake! SNAAAAAAAAAAAKE!" - Campbell

"If they can make it, we can break it" - Chris (Resident Evil: The Umbrella Chronicles)

But now I know that I must go... Back... To the mansion!

Another favourite of mine:

"I GOT A PRESENT FOR YA'!"
-Commando (C&C)

I just thought of another one. In Halo 3 in the second mission.

Marine 1 : Hey, open up!

Marine 2 : Password Please.

Marine 1 : You gotta be kidding me! What password?

Marine 2 : The password so we dont open the door for brutes!

Marine 1 : Do I sound like a brute to you?

Marine 2 : Well you could be held prisoner by brutes.

Marine 1 : If I was held prisoner by brutes, and knew the password, then the brutes could just force me to tell you the password and you would open the door for them.

Marine 2 : ...ok...Well now im defintiely not going to open the door.

Marine 1 : But we need ammo!

Marine 2 : Well why dont you go ask your brute budies then?

This is actually only one version of the conversation, and the voices of the marines are done by two of the makers of Red vs Blue.

Teleios:
No One Lives Forever

Thug 1: Criminal sociology is a hobby of mine. I think it's important to understand not just the individual, psychological roots of one's behavior, but also the social circumstances that foster that behavior. Whether we like it or not, we are shaped by our environment.
Thug 2: Surely you're not suggesting that individuals aren't accountable for their actions.
Thug 1: Oh, no, of course not. Just because we are products of the societies we're born into doesn't absolve us of personal responsibility. Our religions and laws teach us what is right and what is wrong. Frequently, the right choice is the more difficult path to take. It requires sacrifice, self-discipline, patience ... virtues that many of us find somewhat lacking in our natures.
Thug 2: But what if you're born into a hedonistic culture?
Thug 1: Look across history. The reason hedonism is discouraged by most religions and governments is that it weakens a civilization. It breeds sloth, petulance, degeneracy, and selfishness. A divided nation is a fragile nation, waiting to be conquered. Unity is strength. Humans instinctively fashion order out of chaos. It is a natural, probably genetic impulse. Therefore, even an individual born into troubled times has the capacity, and even the duty, to behave in a manner that promotes unity, however difficult it may be.

That's some damn good philosophical dialogue. It can certainly be applied to situations in real life. Never played the game in question, but coming from two random thugs, that conversation's priceless.

First off, any lines from HK-47 in the KOTOR games.
Then one time in fallout 2, during a karate tournament a dude targeted my groin and got a critical hit the whole while the text above his head read "Chop-sake".

anything from any duke nukem to be honest

"blow it out your ass"
"eat shit and die"
"your an inspiration for birth control"
"balls of steel"

and my personal favourite

"damn, dont have time to play with myself"

Most of the dialog in Portal cracks me up....especially the stuff about the cake ;)

There's a horde of funnies in any of the Ratchet and Clank games, too. I won't recount them.

The one line that always sticks in my head is an old Duke Nukem line "it's time to kick ass and chew bubblegum......and I'm all out of gum"

"it was as far as i could fall, it was low as I could go, way past oblivion, to a point only described, as negative zero."-ash from Vampire the Masquerade Bloodlines

some of the best lines from Vampire:Bloodlines

"You could tag-team with Jesus and you'll still going down!"

"You look familiar. Were you ever on a milk carton? "

"The Sabbat ? The Sabbat is worthless, man. Fake tits on a zombie worthless. Fun to watch though. Like the Three Stooges with chainsaws"

What about Dante talking to Cerberus in DMC3?

"In a dog show, you'd definitely take first place"

Here's the YouTube link (1:15)

Advance Wars Dual Strike -

Jake: Get the plates, 'cause you just got served!

Someone missed out an RE4 quote: "Not enough cash, stranger"

Rent:
"Somebody set us up the bomb"

Cuz we can close the thread after i post this, there is nothing who can beat that one! Not even a ninja bear with lazor claws!

Edit - Source : http://www.youtube.com/watch?v=qItugh-fFgg
I really dont know the name of the game :(

Zero Wing.