The guy in I wanana be the guy.

The tank is second, as The guy isnt on the list.

Either the Regenerators from Resident Evil 4, the Pendelums in Silent Hill 3, or Akuma in Street Fighter III on max difficulty.

Super Mutant Behemoths ran into one with a few grenades and a laser rifle, that was one hell of a fight.

The tanks are rather tough, especially when you play with people lacking the sense to run the hell away whilst firing sporadically and not getting crushed and battered to death.

All the options on your poll are easy. The Senate on Rome: Total War is pretty hard, if only because it takes so long.

Darknuts/Iron Knuckles from Zelda, especially when there are more than one of them. They get me into "Oh fuck" mode more than anything.

I've dealt with more than my fair share of Big Daddys, I know how to handle them.

Bought left 4 dead with the holiday discount and I have to say... I simply can't not add a creature that can take 2 clips to the head and still punch me into the ground like a nail.

actually, I really hate Hunters from Half life 2. It's the way that they soak up a WHOLE CLIP from the pulse rifle, and then throw you into the path of a strider.

other enemies in this category include... erm... the bosses in the new prince of persia? actually, that game makes me genuinly want to get into fights. the flashing lights, the combos. Pure bliss

EDIT at least the antlion Guard is sort of: 'oh... shit' scary. unfortunately, Bioshock, left 4 dead and RE5 don't curently grace my console, so I can't formulate an opinion very well

The Big Daddy takes it for me over the Tank, mostly because I can run a good deal faster from a Tank.

Nemesis baby.

Why does everyone hate Tanks in Left 4 Dead?
What about the freckin' Witches?

At least Tanks won't INSTAKILL you if you startle them. (on Max Difficulty)

While Witches can be usually avoided sometimes you find her sitting down crying in front of a fucking switch you need to hit...

Also
CYBERDEAMON FTW! :D

Deathclaw

There is no creature as deadly... no sight as horrifying as a Deathclaw leaping out of the shadows and swiping a chunk out of your torso. Deathclaws in the first Fallouts were bad enough... nothing could have prepared me for my first encounter with one in Fallout 3. Nothing except, perhaps, my Plasma Rifle and a fistful of Bottlecap Mines. Unfortunately I had neither of those at the time.

CyberAkuma:
Why does everyone hate Tanks in Left 4 Dead?
What about the freckin' Witches?

At least Tanks won't INSTAKILL you if you startle them. (on Max Difficulty)

While Witches can be usually avoided sometimes you find her sitting down crying in front of a fucking switch you need to hit...

Witches can be one-shotted.

RobinHood3000:
Witches can be one-shotted.

Uuuh, how?
I used the Sniper Rifle on a crying Witch and aimed and I swear to God I shot her on the face and yet she came at me and killed me instantly.

I don't think it's even possible to kill her with one headshot.

First thing that came to my mind:
Titans, from Unreal. One hit kills are just so damn painful sometimes.

Second thought: Berserker, from Gears of War.

Then I thought of the dogs in CoD4. They REALLY just want to bite your throat off.

Oh, and those sand wolves or whatever they were, in Prince of Persia The Two Thrones, who keep stealing your sand and leap at you the whole time. Not THAT hard to beat, but really frustrating if you mess up a few times, and notice way too late that you're out of sand to rewind time.

Might think of some others later on, but for now, Titans are still my numero uno.

Mr X from the second play through of resi 2.

Just for the fact that he could do something no other enemy could do and follow you anywhere. He could even break through walls something that at the time broke both the series rules and was impressive graphically. Unlike other resi enemy's, you rarely had any clue of when he was going to appear, making you hoard ammo even more making an otherwise easy game (on very easy and easy mind) more challenging as he could absorb ammo like a bitch.

Metal Gear!

Half Life 2 / Episode 2 Hunter Chopper. Rains down gunfire while you desperately try to avoid it. Probably takes up at least half a chapter in each game.

The final "X" encounter in Metroid Fusion scared the shit out of me, although that might have something to do with me being a few years younger at the time.
EDIT:

CyberAkuma:

RobinHood3000:
Witches can be one-shotted.

Uuuh, how?
I used the Sniper Rifle on a crying Witch and aimed and I swear to God I shot her on the face and yet she came at me and killed me instantly.

I don't think it's even possible to kill her with one headshot.

There is an achievement for it on the 360, so I'm pretty sure it is possible.

Queen Gohma in The Legend of Zelda: Ocarina of Time.

Because I am incapable of defeating this giant spider I have never seen Hyrule field.

Yeah, it would be nice to be this skilled at the game, but I am utterly useless...

The Tank, if only because one of them killed me with the Safe Room door, THE DOOR!

CyberAkuma:

RobinHood3000:
Witches can be one-shotted.

Uuuh, how?
I used the Sniper Rifle on a crying Witch and aimed and I swear to God I shot her on the face and yet she came at me and killed me instantly.

I don't think it's even possible to kill her with one headshot.

You sneak up behind her with the Auto Shotgun, then when she looks round at you shoot her in the face at point blank range. On your own this can only be done in easy and normal (from my experience), in advanced/expert you will have to hit her again before she stands up. Or two of you can sneak up and blast her at the same time, as long as you both aim for the head one of you will get the achievement.
But you need good communication, timing and Auto Shotguns.

fix-the-spade:
You sneak up behind her with the Auto Shotgun, then when she looks round at you shoot her in the face at point blank range. On your own this can only be done in easy and normal (from my experience), in advanced/expert you will have to hit her again before she stands up. Or two of you can sneak up and blast her at the same time, as long as you both aim for the head one of you will get the achievement.
But you need good communication, timing and Auto Shotguns.

Actually, it can be done with the Pump Shotgun, as well. And yes, there is an Achievement for it, so it's certainly not impossible.

http://www.youtube.com/watch?v=2M0EbYuzJBc

if we are talking any game then it would be

POKEMON FIRE RED: ELITE FOUR/FIVE

though the short skirts make it all better ^^

Tank on Expert mode is the single most batshit insane monster of the last 5 years of gaming.

Its going well and GRRRAAAA! Oh shit, SET IT ON FIRE AND EVERYONE FUCKING LEG IT! The goddamn thing might as well be immune to bullets but that doesn't stop two of them coming at you in one save point, three potentially on a finale.

LoopyDood:
I Wanna be the Guy's Moon. Freaking evil.

I have bested fruit, spike, and moon! (and frankly the fruit was the worst to me. Every time I walked into a room with fruit in it, I was all, F this, and I went the other way).

METROIDS! They scare the fuck out of me. They're incredibly persistant and even when you freeze them they don't stay down for long. After Metroids I'd say Dr. Salvador, very aggressive and can insta-kill you.

Pyramid Head... OK he's overrated... only a little... look he's just too hardcore, you cannot deny him. You can't kill him either... or at least not until you acknowledge some problem abotu yourself, then he still has as much health as god! Not to mention he comes in pairs!

Jamash:
Deathclaws in Fallout 3 can be pretty annoying, especially if you don't use the Dart Gun, since they can close the distance on you faster than you can take them out, and if you get corned by 2 or 3 of them you might as well reload and save some time.

Definitely but i would also have to add the super mutant behemoths.

The Robot on the moon in Mighty Morphin Power Rangers (SNES). After you kill the damn thing it revives itself with full health. Bitch!

Biggy Man from Splatterhouse. He has chainsaws for hands...YOU CANT TOP THAT!!!

I'm glad someone mentioned System Shock 2's nurses. Kinda made me think of Silent Hill's nurses, but SS2's were better. Hell, the damn monkeys were scary too, that whole damn game was, pretty much everything had you shooting at shadows, but those damn nurses were tough and with SS2 being a true survival game and ammo being scarce, they were a real threat. At least with big daddies you can infinitely respawn, there's plenty of ammo and EVE, not to mention it only takes the tiniest amount of care to not set them off. You can chose to engage them only when you're ready, so they're hardly 'oh shi-' moment worthy.

However, Bioshock does have my winner- the plaster spider splicers. Fort Frolic is full of plastered corpses posed in macabre dioramas so they blend in perfectly, happy to pause and imitate the common statues. Some of those motionless, indestructible dioramas on your way into a room may come alive as a nasty collection of plaster splicers when you return, and all of it performed in the eeriest of silences. Sure, they're not the toughest enemy ever, but they creep they hell out of me and have one of the best weapons on their side- surprise.

coldfrog:

LoopyDood:
I Wanna be the Guy's Moon. Freaking evil.

I have bested fruit, spike, and moon! (and frankly the fruit was the worst to me. Every time I walked into a room with fruit in it, I was all, F this, and I went the other way).

Heh, when the moon first attacked me it scared the crap out of me. The fruit was also pretty brutal.