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Tear Jerker: inFAMOUS 2
The good ending. Cole not only kills himself, but every other Conduit in the world. It stops the Beast and cures the plague, and Cole is finally hailed as a hero. Too bad he'll never hear a word of the praise.
It doesn't help that the last scene in the game with this ending is Zeke narrating a comic book cutscene about all of this, emerging into a crowd of people at one point carrying Cole's now dead body. By the end of the scene, where he's standing on a boat, beside a coffin, as it drifts off into fog, I couldn't help but cry. "Sometimes, I hear folks talking about humans and Conduits like they're totally different. That's bullshit. Cause there ain't nobody with more humanity than Cole Macgrath. I love you, brother. And I'm sure going to miss you."
There's a minor Tear Jerker in the good ending that may be overlooked by most. Throughout the game, a phrase in bold white text will occasionally pop up at the top of the screen, telling you what your current objective is. During the final scene of the game, as an obviously very reluctant Cole stands in front of the defeated Beast, holding the RFI, the game instructs you to hold down all four shoulder buttons at once to activate it. Once you've done so, the objective simply reads "Let go".
Don't forget Kessler. While his methods were extreme, it is worth bearing that this was a man who ran away from The Beast to spend a few years with his family. And upon gaining time travel powers, he went back in time and was forced to murder the woman he loved so as to turn the man he used to be into the kind of person who could save the world. While there is no way to forgive him for what he did, it isn't hard to imagine that he would probably feel it was worth it. And from what we knew of Trish, she would likely feel the same way.
Kuo and Cole's dialogue when he's about to use the RFI:
Kuo: Do it...
Cole: It's OK.
Kuo: It's not OK. You made the right choice. Hell, even Nix made the right choice. I was... I'm scared.
Cole: I am too.
Hell, even the evil ending is a huge tear jerker. First Cole has to kill Nix, whom he's been helping most of the game.
The worst is the way the lines are delivered before that:
Cole: Half as long...
Zeke: ...twice as bright.
Zeke: I gotta try.
Cole: I know.
Oh, and the final cherry on the depression sundae? The Beast, whom everybody had thought to be Chaotic Evil up until comparatively recently, finally gives in and admits that he can't live with what he's become and what he has to do, even if the destruction's in a good cause. And during this scene, the gigantic lava-skinned monster is leaning against the wall of the cathedral, hanging his head and looking every bit as tired as he claims. Yep, for just about everyone in the endgame, Being Evil Sucks almost as much as being good.
The evil ending: Cole becoming the beast makes all of Kessler's (Cole's) efforts to stop the beast and Trish's death in vain. A bit like the fall of Anakin Skywalker.