This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Resident Evil 2
The apparent death of Ada Wong.
Which in the A scenario, has probably the saddest piece of music in the game. It captures the utter grief and anguish of Leon perfectly. He holds his head and falls to his knees in complete despair. Before then, he'd promised her many times his duty as a cop compels him to protect her, only to lose her before the end.
In fairness, most RE fans have a high tolerance for this. Of course, the novelization of that scene hits a lot harder, mostly because we as readers have gotten to hear a lot of Ada's thoughts over the course of the story, and have consequently grown more attached to her as a character.
Sherry meeting her almost dead mother in Claire B.
While playing one of the saddest pieces of music  in the entire series.
The police station notes and logs mostly combine this and Nightmare Fuel, as they tell how the police officers make repeated, desperate attempts to escape or fight off the monsters they are facing, with one officer's log ending with him about to commit suicide.
If you read his file in the third one then the death of David, mentioned in a report found in the police station, become this. He was Driven to Suicide, vowing after a 'staff meeting' (the police officers regrouping to discuss what they're going to do about the zombies) to blow his brains out due to letting a coworker who saved his life at his own cost die due to being a coward... but the meeting was attacked by the zombies and he was torn to shreds.
The fact that the entire Police Station had prepared a welcoming party for Leon, a new guy probably none of them had ever met. You can tell that (demented Chief Irons notwithstanding) this cozy small town police station would have been an awesome place to work at just because of the camaraderie. Then of course, T-Virus happens, and you spend the rest of the game eliminating the walking, cannibalistic carcasses of the very people who were dying to welcome you into the force.