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 and Carver's reaction to the Hunters, which mirrors the player's.
Isaac: (after narrowly escaping several regenerating Necromorphs) God, I hate those things....
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?
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. *drops corpse back on the ground*
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
Isaac has bad history with giant drills. If there'll be Dead Space 4, upon seeing giant drill, Isaac should turn around and go away careful to not touch anything.
Isaac: I'm trapped and the drill is trying to kill me!
Starting a New Game+ means you get whatever weapon you were holding at the end of the game in place of the pistol Carver hands you. This can cause slightly ridiculous situations, like Carver tossing a civilian an assault rifle with an underslung grenade launcher, or complete absurdity, like Carver handing him a Ripper that sets everything it touches on fire.
Or the Devil Horns.
Near the end of the game, Jacob Danik gets mad at Isaac for "meddling in powers [he] doesn't understand." Isaac's response?
In one of the optional (two-player-only) missions, you come across a child's banner for a birthday party. But instead of saying "Happy Birthday," it says, "Daddy Hates Me." The surreality of the message (including its cutesy font) achieves a kind of Black Comedy.