Farmer: I can't take all the credit. My wife handles the business side of things. She has a good head on her shoulders!
PC: Hmm... Really?
During Act III while a demon ambush is going on, the recruits are panicking. Their commander...not so much:
Captain Haile: Private, if you need to be reminded which end of the sword goes where, you haven't been paying attention!
Captain Haile: You there! Damotrius! Stop moping about! If this was your funeral I'm bloody well certain you'd have been told!
And when you're battling demons with him in the Blaze of Glory event at Rakkis Crossing:
Captain Haile: Those worms have come up from behind! Bloody adorable! They're trying to ambush us!
Also from Act III, when raising the last catapult from its moorings, your sole NPC aid comes from a grizzled lieutenant whose vinegar-laced "encouragement" straddles the line between hilarious and Crazy Awesome:
Lieutenant Clyfton: I'm sorry, catapult, I'm not strong enough to lift you on my own. Would you mind convincing my friend over there to lend a bloody hand?!
Made even funnier after you finally get the damn thing lifted, and he becomes amazingly sheepish:
Lieutenant Clyfton: Done! I...uh...promised Captain Haile I'd watch my temper. Do me a favor and don't tell him that I shouted at you a little, all right?
In Act I after rescuing Cain, you can stumble upon a conversation between a villager and a tired patron in New Tristram:
Villager: You know what would take everyone's mind off their troubles? One of Theodas's great comedies.
Barbarian: Yes. My people were the guardians of the Worldstone.
When the old soldier and his wife at Bastion's Keep in Act III aren't being heartwarming, they're usually being funny instead. In particular, after one event they reminisce together about the time she was kidnapped by barbarians: the soldier describes how he was beside himself until they returned her with an apology, and his wife comments that their leader still sends her a bundle of hides every year and is the nicest kidnapper she's met.
Kormac the Templar's truly over-the-top reactions upon encountering Elite Mooks. Made funnier when made against elites in Whimsyshire, the land of unicorns, cuddly bears, flowers and happy clouds.
BY ALL THAT IS HOLY! Do you see that enemy over there?!
In the Caldeum Bazaar in Act 2, there are two kids (a boy and a girl) running around with their pet rabbit. They eventually make their way to an Iron Wolf in the center of the map, where the man kills the rabbit with his sword, splattering blood all over the ground. The boy and the girl then run in opposite directions, crying.
Taking Lyndon through the bulk of Act 2 or 3. His endless complaints are rather amusing...helped greatly by his voice actor's excellent work.
Eirena: Do you ever feel like you are encased in webs and slowly suffocating in a lightless cave? Because I do not.
And there's this little gem of conversation in Adventure Mode between Tyrael and Lorath Nahr:
Tyrael: My stomach feels strange. Lorath Nahr: Did you forget to eat again? Tyrael: No. In fact, I decided to get the day's eating out of the way all at once. I kept at it until I couldn't take another bite. Lorath Nahr: Oh, it sounds like you ate too much then. Tyrael: Being a mortal is very complicated.
Veteran Demon Hunter Greyscarr never shows up in the game proper, but the flavor text for some of the Demon Hunter's abilities imply that he has a wicked sense of humor.
Blood Vengeance: If it bleeds you can kill it. Kill this one slowly.
Archery: Feel the weight of the crossbow in your hand. Now... the wind, the distance, the target's speed. Good. Now try it with blood in your eyes and a demon at your throat.
Sharpshooter: Every creature has a vulnerability. Find it, and put an arrow in it.
Ballistics: How should I know who first invented these devices? Just make sure the correct end is pointed at the enemy and they'll do the rest.
In Reaper of Souls the player encourages Kormac to tell Eirena how he feels about her. Kormac does by asking her if she'd like to continue adventuring by his side after the current quest is over. Eirena excitedly tells him yes. And then she tells Kormac that she feels as close to him as she did to her sisters. Kormac is... less than thrilled when she says that.