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Tear Jerker: Resident Evil 5
Despite 5 being so actiony, what really got to this troper was after you fight Jill. She admits that she couldn't control herself and was forced to do horrid things. And you see part of that when she's wearing the bird mask, like infecting the first Uroboros victim.
Oh, heck, the whole scene with Jill after she's freed of the control device. She seems so physically tired and so very very sad... Maybe it's just a male thing, but that brought out all of this troper's protective instincts. Seriously, she might as well have had "Needs Hug Badly" written on her forehead.
How about the people in the Uroboros facility in those pods? They are all people kidnapped from all over the world to be experimented on. If they're rejected, their bodies are dumped out. That one conveyor belt, you know that one, where they jump up to kill you? They're the experiments that are being dumped out. Mixing Tear Jerker and Nightmare Fuel together, they will never see their families again, are probably in agony, and half of them are being incinerated alive.
The same happened to personnel in the labs. You can find an e-mail in which a scientist is glad to return soon to his friends and family. A couple levels later you will find a report on how all who worked here were put in coma by sleeping gas, terminated and cremated. Yes, everyone, including that scientist.
I'm not gonna lie, when I went through the conveyor belt with the test subjects, I flipped the switch to stop it, but then stopped and thought about the agony they were in...and flipped the switch back on to bring them the peace of death.
What makes the Jill battle even more tearjerking is if you're playing as Chris and hit the action button (Square on the PS3, X on the XBOX 360, F on the PC) Chris begging Jill to stop this, but all the while she tries, but can't until Chris or Sheva rip the device off of her.
The music doesn't help either; it's exactly the sort of music I would think of if I were forced to fight my loved ones.
The track in question is called "Sad but True".
Speaking of RE 5, remember the documents you can read? How about Village Youth's Diary? It describes how people from the village became Majini through the eyes of one of them. Extremely sad and depressing tale which ends with a storyteller becoming Majini himself.
When you finish Lost in Nightmares, you will be showed the cutscene where Jill throws herself through the window, bringing Wesker with her, to save Chris's life. After the latter reaches out for his partner and calls out her name, you are rewarded with the results screen which has him doing just that with great sorrow visible on his face. The music doesn't help either, because it ends up doubling as a sad music of a sort.