Climax of Mother 3.
This.
Tears.
Every single time. I've played the game like, four times, and I cry so hard every time. (I mean. The game's tagline is "Strange, funny, and heartrending" for a reason.) All of the other events in the game (Chapter 1, 6, etc) result in just mass D:ing, but my god.
I can't think of anything that's hit me as hard as that.
Anju and Kafei is also pretty heartrending though. Especially the last part. ffffff