This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Resident Evil 5
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.
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.
Remember the documents you can read? Specifically 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.
Excella getting betrayed by Wesker and transforming into a monster.
When you finish Lost in Nightmares, you will be shown 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.