The ending. Especially considering how the first game ended.
Isaac: sits in the shuttle cockpit, unwinding from the day's events. A look of apprehension flashes across his face, as he recalls the ending from Dead Space 1. Ominous music plays, he hesitantly turns his head...''
Ellie: [sitting idly at the controls, sees Isaac staring at her] ...What?
This little exchange.
Ellie: It looks like the Necromorphs are starting to swarm into the Ishimura, through the Medical Bay. Thankfully, you don't have to go through there. PA: Unexpected Obstruction ahead. Emergency stop initiated. Welcome to: The Medical Bay. Isaac: Crap.
Hot wiring the drill. Ellie calls out that she thinks she's fixed it and Isaac doesn't get a chance to correct her.
Ellie: I'll try to get it started from up here. Isaac: (under his breath) Or maybe I just rewire it from down here... Ellie: What was that? I didn't hear you. Isaac: Uh, nothing. Nothing.
Ellie: Hey! I got it! Isaac: Uhhhh- Ellie: Isaac! Hurry up and get on!
This little exchange off-screen between Ellie and Stross after Stross has stabbed out Ellie's eye with a screwdriver - she's not happy, to say the least:
Stross: The patient's not cooperating! Ellie: Fuck you!!
The reward you get for beating 'Hardcore' mode. Ever wanted to fight necromorphs while acting out the playtime of a 10 year old boy? Well now you can!
When Daina's attempt to capture Isaac get's interrupted by the EarthGov Gunship, keep an eye on the Unitologist goon still trying to hold Isaac in place. His expression when noticing that Isaac has a suit that is space worthy(for a few minutes anyway) while he doesn't is priceless, considering they're getting sucked into space. Made all the more funny when Isaac stops fighting him, looks at him, the goon looks at him in fear, and Isaac proceeds to deck him in the snoz. You can almost imagine Isaac saying, "Really man, really?"
All of Isaac's and Ellie's scenes in the mines. From their banter on who really got the giant drill started, to how much fun he's having fighting off waves of Necromorphs ("Oh yeah, fun times"), Ellie apologizing about having to mine through more goo, and then this crowning cherry:
Isaac: So how do we get in there? Ellie: Straight ahead. We do have a giant drill. Isaac: You know I'm riding on top of this, right? Ellie? Ellie? Ellie!Ellie! [cue rumbling and cut to Isaac launching face-first onto the ground] Isaac: Holy crap, that hurt. Ellie: We can compare bruises later.
This earlier exchange:
Isaac: You're CEC? Ellie: Heavy equipment pilot Class 4. You? Isaac: Engineer. Ellie: *nods* Nerd. Figures.
In Chapter Eleven, a drag tentacle grabs you and pulls you through a hole out into space. As you are pulled, sparks fly everywhere as stone makes contact with your suit. However, you could be wearing the Hacker Suit, which is only a jacket and jeans, and still get sparks flying everywhere. Why? Because Isaac is literally Made of Iron!
Marker-Nicole: Thank you Isaac... now, time to die. Isaac: What? Isaac: *earlier* But Stross said we could destroy the Marker! Marker-Nicole: Not if we consume you first! Isaac: GODDAMMIT I TRUSTED YOU! YOU KNOW WHAT? FUCK YOU! AND FUCK YOUR MARKER!
It's hard to tell if it was intentional, but at one point in the Unitology recruitment center, there is a window that is rather difficult not to shoot out, causing a decompression. If you fail, a shutter will bisect you. At the same time, an automated voice is soothingly speaking propaganda. So, as Isaac lays in half on the floor, the last thing you hear (or see in the subtitles) could be:
Have you ever felt like you were meant to be a part of something bigger?