The last moment in Infamous 2, when you're first told to hold R1, R2, L1 and L2 (basically forcing the player to clutch on to the controller as tightly as possible) and then told to 'let go', is still one of favorite bits of controller-to-game interactions. On-the-nose but effective! And it's a moment that's a bit unique to games because of the way it involves the player.
It's somewhat misplaced in a game with such wanton destruction but it still had emotional impact. Before the last half-hour of the game, I was certain I wanted to replay the whole storyline to see the other/evil side (as a sidenote, it's one of the reasons I hate the absolute light/dark side moral choices in games).
But after that ending, I didn't want to. It was just so well executed that I didn't want to spoil my experience for the sake of completion. I played a bit more Infamous 2 after that ending but story-wise, I was done. I thought it was the perfect epitaph to Cole's troubled life and if they ever make another Infamous, it had to be with a new character.