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.
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.
In one section of the hospital ward, as Isaac gets up after dealing with the Slasher that pinned him down, you can hear a faint sigh and a flatline suddenly going off at one of the nearby beds; the man's last breath. You can never see this man move.
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.
Early in the game, not long after finding your first upgrade bench, You get into an elevator that suddenly grinds to a halt and the doors open to reveal that it's halfway out of a floor and some poor S.O.B is desperately trying to scramble in, begging Isaac for help. Before you have time to react, a Necromorph limb spears him through the chest and drags him off, still screaming and trying to get away, either to kill him or bring him to an Infector. There's nothing you can do to save him.
Men. Women. Children. None are spared from the horrors of the Markers. And this game does everything it can to brutally hammer that fact into your head, from having to cut down scores of necromorphs that were once children and infants to an audio log you can find of a woman screaming at her husband in grief-stricken rage over what she just had to do.
I hope you're happy. I never wanted to come here, but you had to drag us to this shithole! And now look what's happened. My baby girl turned into... something... I had to... How could you... How could you leave us alone!? Do you hear me!?I HAD TO KILL MY BABY GIRL!
Titan Elementary School: Although it is arguably the absolute creepiest part of the game, it's also horrible to think how even innocent children couldn't escape Necromorph 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 a joyful voice. The scene ends exactly as expected.
In the corner of the gym, there are shoes, toys and countless little blood hand prints on the wall and floor. It seems many of the kids were trying to escape and were cornered there, slaughtered mercilessly without any hope of escape.
The story and fate of Howard Phillips, the administrator of Solar Array. He was a lonely man who was locked and imprisoned by local administrative A.I and suffered great depression, until he was killed during the Necromorph outburst.
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. Her reaction upon having to go back into the place it happened is hard to watch.
Ellie: Shit, Isaac, just... Shit. Isaac: Hey, take it easy. It's alright- Ellie: No, it's not alright! I was here this morning with a crew of thirty people. And we were overrun. And before I knew it, they transformed. I had to cut the arms and legs off my friends just to escape. I'm sure there's still pieces of them around here somewhere... Isaac: Ellie, I know. I'm sorry. Ellie: ...and here I am again. I've just walked one bigfuckingcircle today.
When you go into the factory Ellie escaped, you find audio logs from Kaleb, her shift leader. Even as Ellie begs Kaleb to get up and escape, he simply can't and is overrun.
Kaleb: This is Kaleb, from Shift 1. We lost.
When Isaac has to go back onto the Ishimura, he's very clearly hesitant and terrified of going back on, something that Ellie catches onto.
Ellie: You alright? You sound nervous. Isaac: Last time I was here, things didn't go so well...
Marker!Nicole's taunting and guilt-tripping becomes particularly vicious on the Ishimura. Taunting him about Nicole's last moments, how afraid and alone she was, and how Isaac will never know if she simply stayed dead, or came back as a Necromorph.
Marker!Nicole: You can pretend not to be bothered, but being here rattles you, doesn't it Isaac? All this plastic and tape covering the scars - trying to hide the blood and the bodies so no one will ever know. But you remember what happened - no matter how deeply you try to bury it.
In an odd way, the fate of the USG Ishimura itself. The spaceship went from being one of mankind's greatest achievements and the savior of humanity in the Dead Space universe for over sixty years before becoming a derelict ghost spaceship after a horrifying series of events wiped out the entire crew and drove its few remaining survivors into insanity. By the time Isaac returns to the doomed vessel and explores the ruined spaceship, the Ishimura is a shadow of its former self with Necromorphs roaming around on the ruined spaceship once again, parts of the superstructure having decayed into ruins, and the mysterious ghost-like whispers Isaac deals with during his harrowing return.
At the beginning of Chapter 13, 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 realizes what's happening, she starts losing it at Isaac and starts begging Isaac not to launch the ship.
Ellie: No. No! No, don't you dare, don't you dare launch this ship! ISAAC!
Just listen to what Isaac says during this moment. His comments about how he couldn't save Nicole but he can at least save Ellie really stabs the heart. After everything he's been through, Isaac clearly feels like he's failed time and time again to save anyone, and though he doesn't want to be apart from Ellie, if he can save just one person...
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.
Turns out Tiedmann was a good guy who was doing what he had to do and he just so happened to be 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.
This point, when taken into account with the "Previously on Dead Space" monologue, actually perfectly illustrates the darkness of this story. People like Tiedmann got involved with the Markers in hopes of saving humanity from its looming extinction as a result of thoroughly exhausted resources... Unfortunately, this is exactly what the necromorphs planned, using a race's desperation in order to spread and destroy them. Men like Tiedmann only wanted to save humanity, and all they accomplished was effectively hastening its destruction.
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."
Dead Space 2: 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 "Goodbye, Lex. I love you."
Ellie: No. No! No, don't you dare, don't you dare launch this ship! ISAAC!