The humor in Pokemon games generally comes from the names you give people/Pokemon.

Edit - Also from really, really dumb logic.

True, but there are quite a few in-game quotes that developers put in there that are really quite funny. Youngster Joey is always a fan favorite.

Quest for Glory series! very amusing humor!
especially the death messages!

Portal 2 is the funniest game i've ever played.

One game i played that takes itself way too seriously is Assassins Creed 3, it almost makes a joke out of itself.

well.. i can't remember all the games that made me crack a few laughs here and there but what comes to mind is:
Bayonetta
Ratchet and Clank Future
Gravity Rush
Uncharted: all the main entries
The Cave.

There´s no game that beat the humor of THIS:

Did you play it?

Humor isn't something I see in game. But Mass Effect games and Splinter Cell Chaos Theory have very funny lines and dialogue. Sam Fisher has great humor in chaos theory.

The Monkey Island series for sure.
Zelda games are pretty funny too, especially Minish Cap.

Jade was the best character in Tales of the Abyss.