This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / [PROTOTYPE 2]
The final conversation between Alex and his sister, Dana after Heller absorbs him.
Alex: This is no one's fault but your own—you do understand that.
Dana: I understand that I had a brother once: a boy named Alex. A boy who used to play games with me, and go skating with me, and watch scary movies with me. I understand that... Alex is dead now.
Alex: I am no longer bounded by "life" or "death", Dana. I've moved beyond that. Heller has as well. He just doesn't know it yet.
The mere fact that Alex Mercer actually died. For anyone who's played the original Prototype and grew attached to him, this is really depressing. Alex doesn't even seem upset that he was defeated and actually laughs.
And it doesn't even help any if you factor in the Jumping Off the Slippery Slope. Original Alex was a horrible person. Blacklight!Alex finished the first game wanting to be a better person, and started Walking the Earth to try and achieve that. But instead he found so much betrayal and hatred he became completely fed up with humanity and became pretty much exactly what he hated so much in the first place.
Father Guerra's death. Heller is just as devastated as the player.
A remarkably subtle one from Blackwatch, of all places. While Heller is masquerading as a member of a patrol in a Red Zone, they chat amongst themselves, a standout being the following (paraphrased):
Soldier 1: Hey, you ever wonder where you'd be without Blackwatch?
Soldier 2: Dunno, man. Probably dead or in prison.
Soldier 1: Yeah...me, too. *silence*
It was in that exchange that Blackwatch stopped looking universally like a bunch of Axe-Crazy psychopaths and actually became somewhat worthy of pity. This troper was reminded of one of the iconic lines of John Rambo:
"For me civilian life is nothing! In the field we had a code of honor, you watch my back, I watch yours. Back here there's nothing...Back there I could fly a gunship, I could drive a tank, I was in charge of million dollar equipment, back here I can't even hold a job parking cars!"
The men that Blackwatch recruits are broken, plain and simple. Some of them don't care, others are blind to it, but the men in the patrol knew exactly why they joined Blackwatch. One way or another, they couldn't function in a world where the Blackwatch Creed didn't apply. And they know exactly where men like that end up when they try to live normal lives.
Sometimes when you're in the Red Zone, you can find a civilian or two on top of the taller buildings. They're standing on the edge. They turn to look at you. Then they hold their arms out from their sides and just... fall backward without a word.