Breath of Fire III pulls this off after the first boss battle. After killing the Nue, you learn it was just stealing food from the village to feed its babies...which were long dead. The Nue didn't realize this, evidently. This sets off one of the game's major themes: is it acceptable to harm others when you have the best of intentions? How about when you're basing those intentions on incorrect beliefs? The game doesn't really dwell on this except at key points, but when it does, it hurts.
It gets worse from there. For one thing, Balio and Sunder show up and throw an incredibly vicious Player Punch very shortly after that.
Also, while it could just be Capcom's Giant Space Flea from Nowhere instincts demanding that just about every important scene have a boss, there are a lot of really likable characters who for whatever reason insist you kill them to inherit whatever power you were there to learn from them.
Among the tragic deaths are: the Nue (see above) the Mutant Plant, The Old Man in the volcano, the dragon spirit (which may have been Ryu's father) Garr's former Guardian friend, Jono the Brood Elder and even the Final Boss herself! The game makes the hero revisit many of these just before the end in case you missed the theme.
The endgame has to be the worst, though. After spending pretty much the entire game searching for Rei and Teepo after being separated in the beginning, and having found Rei again shortly before this, you finally reunite with Teepo...only to learn that he is actually part of the dragon Brood just like you. Unfortunately, while you reject the Goddess Myria's claim that the Brood is too dangerous and their power must be sealed, and are questing against her for this, Teepo accepted that claim and allied himself with her. Cue fight to the death. The game really twists the knife on this one with Teepo's last words after the fight, though. "Ryu... Myria is right... look at us... all the Brood know how to do is fight and kill each other... like this... but... I didn't ask to be Brood... I didn't ask for the power... I just wanted to be with you, Rei, and you, Ryu... my family...." At which point he turns into a dead dragon whelp.
And if you're not reduced to a wreck immediately after that, go camp and talk to Rei. Watch his reaction...