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Tear Jerker: Radiant Silvergun
Stage Five of Radiant Silvergun is an especially tearjerking moment. Unfortunately, the game is Japanese without subtitles, so it can be hard to pick if you haven't read a translation. The entire tone of the game is rather sad, what with you being the last remnants of the human race and all. And then there's the moment where Gai does his Heroic Sacrifice.
It happens all the time, actually. And you'd be surprised at how much someone can change when under threat for total annihilation if they don't reform.
The premise itself. In particular, think of how it might feel being one of a few surviving humans left in the universe, in a starship that barely escaped Earth's xenocide, knowing that you're all that's left, knowing next to nothing about what caused the xenocide in the first place, and knowing that you'll have to return to Earth in a year or so when you run out of supplies? A few humans simply isn't enough to repopulate the human race, so even if they do win against the Stone-Like, there'll be nothing but a dead planet waiting for them.