It depends how you define it really... A lot of the non-po-faced modern games have got good dialog with some nice chuckles in it. A lot of companies have figured out that if you want grown ups who've played a lot of games to buy your stuff, you need to have SOMETHING to get you engaged with the characters. Some of them are just generally well written, while others drop the charade of being so hyper real that no-one ever cracks a smile and go the other way.
Bulletstorm is probably the funniest mainstream game recently. Oh its not a comedy game, by any means. But theres laughs to be had. Funny skillshot names (I'm a fan of 'Ejeculated' when you kick guys out an air lock) and dialogue that although a little freudian is good to listen to. Stuff like 'murder-boner' that brings out the kid at heart. Although I guess its more fun than funny. Certainly beats the strong silent, warrior monk types in other modern games. I'm looking at YOU CoD series.
Outside of that kinda stuff (i.e. just funny dialog) I've had bad experiences with games that are comedy from the ground up. Psyconauts is just awesome ofc (Shafer is a god), but others are less good, often because the devs spent too much time being funny to make a good game. The humor in magicka is great, but it BADLY needs a better control system... unless you have a keyboard with on-the-fly macros you'll give yourself carpal tunnel...
The old point and clicks are indeed probably the best, although again its the dialogs rather than the gameplay thats funny and the core mechanics are solid even if you are doing silly things. Personally, I think that Beneath a Steel Sky is the best of them all ('Wait you'll need a Rad Suit to go in there'... 'Well I think this suits pretty rad') but the others are great too.
Oh and MDK too. Funny game. Also Fallout series (again more dialog and background) and a VERY unloved old game called Take No Prisoners has some fun stuff in the logs you pick up.
