For me, it was probably in Suikoden 2.
What's yours?
Riou/Hero and Jowy team up temporarily to protect Nanami, only to have her die right afterwards. Of course, she lives in the good ending, but still - at the moment it was heartwrenching. Two friends putting aside a massive conflict to fight together again, only to fail to protect the one they love and go back to fighting again in the end. The fleeting nature of their renewed alliance, the desire to protect someone dear to them, finally putting the asshole Gorudo in his place, and the tragic ending of the affair were all massive gut punches of all different kinds. Plus, using Jowy in battle again and seeing how far he'd come was awesome.
What's yours?