VtM Bloodlines, when Beckett asks you “Why do we exist?” if you are a Malkavian you get to say “BECAUSE THE JELLYFISH WILLED IT SO, WHY ELSE?!!!” 
More George Stobbart: “The door was locked. {Pause for a beat} It wasn’t opening time yet.”
From FFX : Upon meeting a giant sandworm : “Where’s the early bird when you need 'em ?”
Upon meeting a really odd creature “Who makes these things, anyway ?!”
From City of Heros : “The Bad Protest is the one with all the head injuries.”
"No, ‘non-violent protest’ does not mean ‘Knives only’. "
From Star Control 2 : Dialogue from here.
For loads of laughs, try playing Arcanum as a mentally challenged adventurer…or even an Idiot Savant (the character was stuck in a home for the dimwitted, but in reality is quite intelligent). My half-ogre always went up to people and introduced himself as “Hi! I not too bright!” The dwarf NPC said something like “Oh, an idiot. May the gods smile upon you and put you out of your misery soon.” The primary NPC, who believes that the PC is the reincarnation of a god and that it’s his (the NPC’s) job to guide the PC around the world, is incredibly frustrated by the PC, and always mutters about his responsibility.
In Fallout 2, one NPC (Cassidy) will occasionally say that he wishes he had a limit break (reference to Final Fantasy 7).
World of Warcraft has a lot of good ones, especially when you get to player emotes. Someone posted on Google video a file with the new /silly emotes for the new races. I blocked out a lot of the Draenei ones though, as they tended to involve gnomes and mating rituals.
Female Bloodelf: I hate going to Thunder Bluff, you can’t find a good burger anywhere.
Male Bloodelf: Don’t you wish your girlfriend was hot like me?
And in the Rend event in UBRS Rend and Nefarious like to shout out random things.
Rend: I want those boots! Don’t touch that corpse!
Nef: Kill the one in the dress!
And of course, from FF1–“I shall knock you all down!”
Warcraft 2: clicking on the Footman repeatedly will yield interesting results.
Join the Army they said…See the world, they said…I’d rather be sailing!
“The Mamushka!”
No One Lives Forever had a bunch of hilarious conversations. One bit I particularly liked took place in a Hamburg nightclub. Your character is Cate Archer, a british superspy. You have just met up with your fellow operative, an uber-macho American named Tom Goodman. The waitress asks if the two of you would like something to drink.
ARCHER: Scotch and soda, please.
GOODMAN: Old Granddad. Bring me the bottle, a tumbler, and a bowl of ice.
ARCHER: Goodness! Are you celebrating?
GOODMAN: Compensating, actually.
ARCHER: How sad for you.
And later, after a botched mission:
ARCHER: Things got complicated.
GOODMAN: I’ve heard that before.
ARCHER: Probably from your mother.
No sir, I can assure you that wasn’t me. You’re both wrong - it was Tellah from 4.
From Sam & Max Hit the Road:
“Mind if I drive?”
“Not if you don’t mind me clutching at the dashboard and screaming like a cheerleader.”
I use that one at every opportunity.
More Minsc:
“Buttkicking–for GOODNESS!!!”
“Evil around every corner… careful not to step in any…”
Somebody else from Baldur’s Gate:
“Stop clicking on me!!!”
Somebody else, who you have to click on to complete a quest:
“Hey, don’t click on me, pal. I don’t want to get involved.”
I can’t remember which unit said this - one of the human units, anyway. The last in the sequence before it goes back to the non-angry confirmations is ‘Why do you keep touching me?’
And the female elven hero unit from the expansion:
‘You never touch the other elves like that!’ and ‘Do that again, and you’ll pull back a stump!’
And, not funny, but fun to say:
‘Dabu!’ ‘Zug-zug.’
From Prince of Persia:The Sands of Time. Your companion through most of the adventure is a princess whom the prince had not met before. If you sit in place with the camera view focused on her, after a while she says “Stop looking at me!” (or something to that effect.)
Baldur’s Gate II : “Go for the eyes, Boo ! Go for the eyes ! SQUEEE !”
From Starcraft, if you click on one of those legged Protoss robots often enough, it says “YOU HAVE TWENTY SECONDS TO DROP YOUR WEAPON”, like ED-209 in Robocop.
From FFVII : “You can’t come in ! Not only do you like to dress as a woman, but you like to smash and grind things !”
From The Legacy of Kain : Blood Omen :
“The wind carried screams from the west. I could not help but smile: someone else in this world was suffering more than I.”
“Nupraptor’s head. Alas, poor Nupraptor - I knew him well. Well, not really.”
"Worms and maggots fed upon his festering skin, the scent of tainted blood seeped through the wounds upon which they feasted. Pity . . . such a waste; good blood gone bad. "
"Vorador’s pantry! A vampire’s feast! Like cattle awaiting slaughter, men and women dangled from the rusted hooks upon the dungeon walls, blood and viscera frosted the dirt and stone. The abundance nearly overwhelmed me. For blood is the life . . . "
“Turning the ring over in my hands, I realized that it was crafted from some strange alloy formed from broken teeth - ground down and soaked in blood.”
Moebius : “I’ve seen the future, Kain ! You die !”
Kain : “But I am dead.” < cuts of Moebius 's head >
“Once I embraced my powers I realized that Vorador was correct. We are gods - dark gods - and it is our duty to thin the herd.”
OMG!!! I used to repeat that all the time in highschool, er, 20+ yrs ago. Wow, now I need to dig out the old C64, I still have all my floppies/games.
Can’t remember if it was Midway/Bally or what, but the arcade game, Sinistar! “Run Coward!”
**Beep. Beep. Beep. Beep.**1
Leonard Nimoy, Civ IV
1: Read as ‘beep’ not as making the sound. I’ve exploited it as my “new e-mail” alert. It’s fun but getting to be anoying
“BERNARD! Don’t be a tuna head!”
“The Tentacle mating call?! AAAARGH!”
Or, from an entirely different game…
“Please don’t think I’m a bigot…I kill all races equally!”
In FFVII, Barret says something like “It may look like an ordinary wire to you, but to me, it’s a shiny golden wire of hope.”
And the many, many lines in FFX that are hilarious only because of the bad acting:
Yuna: said like a high pitched robot I first me Sir Jecht ten years and three months a-go!
Williams, makers of the most badass arcade games around (and a few softballs). Subsequently bought out by Bally/Midway (now just Midway) in the video-game collapse of the '90s.
And as long as we’re going old school, “Chicken! Fight like a robot!” is a classic.
More Baldur’s Gate 2:
The evil mage Edwin talks sex with the evil drow priestess Viconia:
Viconia: Dark alleyways whisper rumors of the prowess of Thayvian men, Edwin. Would this kind of vulgar tongue-wagging be claptrap or truth.
Edwin: This Thayvian male is as red-blooded as his cloak, Viconia. And has left many a concubine gasping under my erotic onslaught.
Viconia gets into it with Jaheira the half-elven druid:
Viconia: Tell me, Harper, who was who with your parentage? Father the darthir, mother the rivvil? Or father human, mother elven? It’s always confusing with crossbred mongrels.
Jaheira: Two people in love, swine. A rain not likely to soak your parade of scabbed obscenity anytime soon.
Nasty!