A rather unique - unique being an entirely charitable word - horror game with comedic themes from the mind of Hidetaka Suehiro. The game follows FBI agent Francis York Morgan's murder investigations as he tries to track down the Raincoat Killer. While it certainly deals with some pretty terrifying elements, Deadly Premonition leverages it with a dash of humor, much of which you're free to drum up yourself, and the open world setting is rife with plenty of contextual humor. If you're looking for a really quirky and out-there title give Deadly Premonition a look.
I think I'm beginning to see a trend here, some of the most successful funny games are otherwise serious titles that are given a breath of levity through humor. The Fallout series is no different, a bleak and violent post-apocalyptic setting dotted with quirky characters, mechanics and dialogue. Humor cleverly invades much of the aesthetics as well, with PIP-Boy and other 1950s-era Americana. Nearly every title in the series is a classic and well worth checking out.
Beginning life as nothing but a joke, Goat Simulator received a surprising amount of enthusiasm when some early footage was released to YouTube. The developers at Coffee Stain Studio followed the support and released Goat Simulator on what else but April Fools Day. They even fixed only the bugs that broke the game, leaving any other potentially funny glitches. The final result is a goofy romp where you run your goat avatar around the map trying to do as much damage as possible and ultimately looking for humorous ways to bug out the physics engine. It's good for a few hours of fun, and new modes and mechanics being patched into the game will make it something worth dusting off now and then for a few additional laughs.