Decluttered my backpack in Skyrim. On a road in the middle of some birch forest in the southeast.
Some guard comes trotting along: "Hey, you can't leave sharp things lying around like that! Someone might get hurt!".
I: *wtf*

I think they also accuse you of littering if you dump it all in a town/city.

(Most times I end up dumping stuff in the middle of a dungeon. There's one place where someone's gonna come across a ton of food and wonder what happened there.)

Sacred and Sacred 2 had plenty of funny quotes on tomb stones and S2 also had some funny ones on start-up.

My favorite was: "Even if you're eaten by a dragon, you still have two ways out".

Everything Glottis says.
Also, it is more of a situational thing, but being told off by the boss for going to the ladies bathroom in Deus Ex.

Mine is from Destroy All Humans 2.

Whenever you are in Japan, when you walk by a civilian, they will go: "You are very ugry!". Has me crack up everytime.

To say that Gogron gro-Bolmog from Oblivion has a morbid sense of humour would be an understatement:

https://www.youtube.com/watch?v=R6S6D46Mp3o

"Evil, meet my sword! SWORD, MEET EVIL!!"

Dragons Dogma, a gobln rendition of "Who let the dogs out"

https://www.youtube.com/watch?v=Mfh6KClkr3o

Watch from .30 sec

I know exactly where this is in the game! i went there and saw him dancing via lyncean sight and wondered what the hell was going on. hahahaha now i have to go back. :)

Indiana Jones and the Fate of Atlantis:
After you (Indy) pushed Sophia to become a "volunteer" for the knife thrower, she survived it and got a knife with blood stains from him, she says: "Here, take this knife - before I use it on you!"

The Secret of Monkey Island:
"Never pay more than 20 bucks for a computer game."

The mercenaries in Far Cry 1

Sigmen Floyd!

Spoilers if you haven't played through Butcher Bay. My favourite and frankly only enjoyable part of the whole game.

Yesterday, Dragon Quest 6: "I hope you like nothing because we have lots of it".

Years ago I played through Mass Effect 2 and was doing Grunt's loyalty quest. He has a few lines that he yells out during combat like "worthless" and "I... am... KROGAN!" Thing is, the second one glitched and played the first one halfway through, so in the middle of the fight he blurts out "I... am... worthless."

Good times. I'd like to think that it's something that a Bioware employee programmed in to be a super-rare-and-totally-on-purpose, but that's probably giving them too much credit.

So whenever someone mentions Psychonauts, you gotta replay it? :D

(Dammit, lost The Game, first time in a couple years I think)