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troperville

Isaac trying to use his stasis module to slow down the automated freeway traffic, which looks like a typical simple stasis puzzle from the previous two games. Except that he only slows down ONE transport, causing the rest to crash in a massive pileup.
Isaac: ......oops.
Isaac and Carver's reaction to the Hunters, which mirrors the player's.
Isaac: (after narrowly escaping several regenerating Necromorphs) God, I hate those things....
Remember the Hand Cannon from Dead Space 2? It's back... as the Devil Horns. It has infinite ammo and is basically a One-Hit KO on anything. But, reload it, and Isaac will headbang.
The Bot Personality Pack DLC for the Scavenger Bot turns your adorable bot into an incredibly snarky rover that has a complement of lines that occasionally goes toe-to-toe with HK-47's dark humor.
Scavenger Bot: Ah, there you are. A gentleman was looking for you. His face was on backwards. And he had bone swords for hands. I sent him your way. I hope you don't mind. He seemed anxious to find you.
Scavenger Bot: Nothing much to report sir. I'll try looking over here. With any luck, it'll be more resources, and... fewer body parts.
Scavenger Bot: What do you do with all of these resources? If you're building weapons to chop even more limbs off people. I'll have no part of it. That makes me an accomplice, we're simply not that close.
Late in the game while in the research facility in cooperative, before you enter the generator room to return power to the sterilization gas to clear a bunch of infestation. Carver and Isaac get this little gem...
Carver: Wait, you're not thinking we should mess with this sterilization system, are you?
Isaac: *almost teasing tone* Mmmmaybe?''
Carver: Isaac, it's gas that eats your face!
Isaac: Come on, what's the worst that can happen?
Carver: It's gas that eats your face!
Near the end of the game:
Carver: Congratulations, you just turned the city into a pretzel. What now?
After the crash on Tau Volantis, Isaac searches desperately for Ellie amongst the wreckage in a snowstorm. As he enters a relatively intact section, he suddenly spies a corpse on the floor. He panics, rushes over and digs at the snow and ice. He then rolls the corpse over and...it isn't Ellie. It's another crew member and half of his head is blown off. Isaac's response?
Isaac: Oh, thank God.
Danik's disbelief that Isaac could still be alive is priceless thanks to the delivery. Instead of the usual anger, confusion, or frustration, he's very... affable about it.
Danik: Isaac, is that you? You are unbelievably hard to kill, are you aware of that?
Whenever Isaac meets Danik Isaac ALWAYS escapes.
Despite the much, much darker tone of the DLC, Isaac and Carver still manage to engage in some humorous dialogue
Carver: Let's get looking, dead boy.
Isaac: That's not funny.
Carver: Yeah it is.
Most of the co-op banter between Isaac and Carver when they run into the giant drill. The end of that sequence has the crowning moment, though.
Isaac: Heh. Jesus, I thought that was it.
Carver: (chuckles) Yeah...(chuckles again) Fuck this planet.