Lunar: Eternal Blue/Tear Jerker

The first ending, where Lucia decides to return to the Blue Star, leaving Hiro to helplessly watch her walk out of his life. Then comes the epilogue, where Hiro decides to FOLLOW HER THERE. Lucia's tears of joy upon seeing him on top of that crystal-thing of her's gets this troper every time.
There's a really big one at the end of Lucia's quest to find the goddess Althena. What does she find? The goddess', aka Luna's, final message, left when she was a grandmother. The moment you see Luna like that, it just hits full-force: Everyone you came to care for and love in the first game...is gone.
- The preceding scene when Nall eulogizes the cast from the first game as well as Luna's sacrifice. Sure we KNEW they were dead, but considering how likable the cast of the first game was, this sequence made This Troper realize how attached he had grown to them.
The entire scene where Ronfar saves Mauri.
The scene where Ruby has to accept the power of the Red Dragon and come to terms with the fact that she'll outlive her friends...Poor dragon-kitty.

Ruby: I don't want it, Hiro...I don't want eternal life!

Wait a second! No love for the first end?
- The Playable Epilogue kind of subverts it, since there's a whole bunch of places you haven't explored yet after that "end", making it fairly obvious that there's more game to come. Lucia heading back to the Blue Star because she's terrified of the idea of Hiro eventually dying (among other reasons) is still pretty brutal, though.
  - Hiro's reaction alone to all of this, and especially his anguished cry as she's fading away, are enough to make you reach for the tissues by themselves. Combine them with Lucia's side of it, and you should be blubbering even before she leaves.