* ''BreathOfFireIV''. Nina's sister/Cray's betrothed, Princess Elina. [[spoiler: Thanks to many nasty experiments, she's been turned into a god-like monster. It's not perfect though, and she's in extreme pain. You start a quest to find the only weapon that can injure gods, and Cray has to mercy kill her. Combined with the MadScientist pulling a KarmaHoudini and you've got tears and anger. It's even worse when you realize this (probably) is a prequel, where the MadScientist perfected his work, and BigBad IS a god-like monster.]]
** It causes quite the PlayerPunch for people who [[spoiler: ''have'' sisters in real life that they love dearly]]. Nina's narration of [[spoiler: "I knew that I would never see my sister again"]] nearly broke this Troper.
** There is also Fou-Lu's companions, who all die in one shape or another to help him escape from The Empire. [[spoiler: The boar who bludgeons itself against a rock blocking a secret passage was pretty moving. But the farm girl who tended to Fou-Lu when he collapsed in her village and blocked the door and stalled for time when soldiers investigated her home to give Fou-Lu time to escape was really bad. Then they captured and sacrificed her to powerup a nuke they droppped on him. Aww man.]]
** [[spoiler: Ershin's]] last stand against the forces of the Empire. [[spoiler: Yes, my tin-can friend...that was an appropriate time to laugh.]]
** [[spoiler:And the massacre of the Chek inhabitants, especially in the manga adaptation.]]
* As above, finding out what happened to Elina and her fate.
* [[spoiler: Ershin's]] last stand against the forces of the Empire, which is UpToEleven. [[spoiler: Yes, my tin-can friend...that was an appropriate time to laugh.]]
* [[spoiler: The massacre of the Chek inhabitants was bad enough in the game, but in the manga adaption, some of the apprentices have warmed up to Ryu a lot and he grows fond of them. Their deaths trigger Ryu's HeroicBSOD and his breakdown before, during and afterwards is just tragic.]]
* [[spoiler: Mami's fate, being used for the Carronade to try and kill Fou-lu. It sets off Fou-Lu's WoobieDestoryerOfWorlds.]]
* Mixed with CrowningMomentOfHeartwarming, [[spoiler: Ryu beating Fou-Lu in their BattleOfTheCenterOfTheMind by showing him Mami's bells that she had in her hair.]]