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  • Trish's death. No matter what you do, Cole can't save her.
  • If you collect all the Dead Drops in the first game, it's revealed that the chopper trying to pick up John when he and Cole first met really was from his agency, trying to pick him up and bring him home. He was so Properly Paranoid by that point he thought it was the First Sons and fled. If he'd left Empire City, he never would have become The Beast, and the genocide in the second game never would have happened.
  • The end of the first mission has Trish breaking up with Cole after learning that he opened the Ray Sphere, resulting in the death of her sister.
  • The good ending Cole realizes that everything he had been fighting for is a lie and he was being used, also that he is not leaving his friend betrayed him and his girlfriend is dead. The part that takes this home is last quote: "I have never felt so alone".
    • The good ending of the second game is even worse. 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".
      • 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.

 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 a Chaotic Evil Complete Monster 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.
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