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Tear Jerker: Dead Space 2
Heavy Spoilers for Severed: Gabe's death in Severed. His leg is blown off and his final moments before death are fighting off a horde of Necromorphs and making damn sure his wife gets to safety before he finally dies. His final words are "I love you."
Lexine's reaction is heartbreaking.
The opening video with Nicole, while not this, adds a really huge emotional kick in the groin. Not only was her being on the Ishimura in the first place Isaac's doing (he'd encouraged her to go on the voyage because she hadn't been sure she wanted to go) and as they're talking, the video begins to cut out...and anyone who played the first game knows that communications from the Ishimura went offline a short time before the Necromorphs began slaughtering the entire ship.
At the beginning of Chapter 13 you Ellie gets on a gunship, Isaac walks over and activates it while she's on it. Before and after he does this you can tell he doesn't want to. When Ellie realized what was happening, her words, in a teary form (yes, it sounded like she was going to cry) where "...You bastard..."
Ellie: No. No! No, don't you dare, don't you dare launch this ship! ISAAC!
Immediately after that, Isaac slumps down to the ground, and Nicole is there. They have a heartfelt conversation about how he simply can't let her go, and then:
Nicole: Isaac. Touch me. Isaac: (pauses, then reluctantly stands up) ...I don't think that's a good idea. Nicole: Isaac, please. Make us whole. Isaac: (looks away) I can't.
The ending, at first. You just see Isaac, alone and miserable, just waiting to die. Then Ellie suddenly comes down to rescue him just to save him from that.
There's an Audio Log of a woman screaming at her husband in grief-stricken rage for convincing her to come with him to the Sprawl, because she had to kill her own Necromorph-ized daughter.
We do get some idea of Ellie's backstory and her reasoning for wanting to fight her way through the disaster on her own, as well as why she's so enraged at Isaac's attempted Heroic Sacrifice; she's already seen most of her crew and friends die earlier on, and the last survivor of that group performed his own Heroic Sacrifice to help her escape.
Kaleb: This is Kaleb, from shift 1. We lost.
Invoked by the video chat between Isaac and Nicole in the intro. Seeing how happy Isaac was in that scene really highlights just how much he's lost as a result of the events in the first game. It's also implied throughout the game that Nicole was one of the only things in his life that actually made him happy.
The scene after Isaac destroys the Titan Marker. The whole facility is crashing down around him, and all he does is sit down with a look of complete hopelessness and despair, resigning himself to death.
Definitely YMMV, as the scene in question can also be interpreted as Isaac, having destroyed the Marker he created, sitting down with a look of distant satisfaction, as in "I did it. It's over."
Turns out Tiedmann was a good guy who was doing what he had to do and he just so happened to horribly wrong about the Marker. We learn that all he wanted to do was save the people from poverty that occurred with the collapse of the planetcracking business and what happened instead was that his actions got countless people in the station slaughtered. He STILL clings to the wish that what he did was right for the people as he shambles toward you with horrific wounds covering half his body. Though, then you get the option to destroy his head with a javelin gun, though at that point it might have been a mercy given that you already had to shot him in the neck with said javelin gun.
Titan Elementary School: Although it is arguably the most creepiest part of the game, it's also horrible to think [Would Hurt a Child how even innocent children couldn't escape Necromorhph onslaught]. Worse, the high number of children Necromorphs and blood splatters around the area suggests that it happened during NORMAL SCHOOL TIME.
In the nursery section of the school, you see a mother who have gone insane and thinks a Crawler is her baby (which could possibly be hers) and tries to cradle it. She continually says "Come to mama!" in joyful voice. The scene ends exactly as expected.
In the corner of gym, there are shoes, toys and countless little blood hand prints on wall and floor. It seems many of the kids were trying to escape and were cornered there, slaughtered mercilessly without any hope of escape.
In Titan Heights, you can hear and see hundreds of civilians in apartment complex who somehow failed to escape. You see terrified civilians trying to escape while being butchered alive. You walk past apartment rooms to hear people are either panicked or being murdered inside. You see people abandon their loved ones to certain death so they can escape. The saddest part is that there's nothing you can do to save those civilians.
There is a point in the beginning when you are passing living quarters. You hear from inside one of them the cries of a baby unattended, endlessly wailing as all the sound of chaos and death goes away. You go further and you hear a woman crying, crawling on the ground towards a gate that separates you from her. It looked like she was crawling to the crying baby which was probably hers. She eventually succumbs to her injuries the same time the baby's cries stop. It is not too far of a stretch to imagine women protectively clutching their babies as they set upon by necromorphs only to turn and rip their child apart. All there is in the Dead Space universe is death and the cold vastness that surrounds you.