This here is actually one of my favorite moments in any video game, from one of my favorite games and what I consider a highly underrated gem. The final battle of Mana Khemia is an absolute gut punch, and the build to it effectively changes the tone of the game in the best way. Obviously, there will be some spoilers.
To start, Mana Khemia does not start off as a game you expect any kind of hard-hitting sad moment from. You play as Vayne, whose father was a famous Alchemist before he died. Living on his own with his Mana, Sulpher, he is approached by the Al-Revis Academy to learn the art of Alchemy. There is no world ending plot, no grand scheme, just the story of a boy learning the craft and forming friendships.
It does get a bit strange when one of the teachers seems to have something against you, though this comes in the form of her convincing a few other pupils at the school to poke and prod at you. You do discover you seem to have a strange kind of power other people don't have, but it's all very localized and small compared to any other RPG at the time, in this case, you revive a tree after it was destroyed, or later on you grant your party strength when fighting a Dragon.
Eventually, this teacher starts to screw with you more directly, and this is when things start to get dark in a hurry. Throughout your stay at the school, you have started to form bonds with people for the first time, having lived your whole life prior to that alone, and suddenly one of the teachers at the Academy straight up murders one of your allies, the one you build the closest bond with (Could be any party member, just depends on who you've been doing events with). Overcome with sadness, Vayne activates the power he showcased against the Dragon and in reviving the tree from before and full on revives the character from the dead.
Finally, you get the answer to what your powers were, you were not a human, but an Artificial Mana. This reveal in particular it has been building for some time, and you realize the Cat Sulpher, who you thought was your mana, was actually just a common house cat you were bound too. This isn't the emotional twist, the twist comes with what your power as a Mana actually is.
There is another character in your party who has a terminal disease of some kind. As you learn, your 'father' was involved in curing her of her sickness using his Alchemy, though due to his own arrogance made a mistake and gave her a different disease altogether, one he couldn't cure, something else the story had been building too.
An artificial Mana was the end result of his work to fix his mistake, and he created Vayne. A Mana with the power to grant you any wish that exists in your heart, but the catch is it's not what you ask of it. It looks deep into your heart to find your true desire, and that is what it will grant. Vaynes father was a man who, deep down, couldn't live with himself for what he had done to that little girl, and so the Mana granted his wish and took his life.
Vayne is, as one would expect, overcome with grief knowing he is responsible for his father's death, and now has to fight with the fact he has this power within him, and the horrible things it is capable of doing. And that's when, once again, his power activates granting him the wish that lives deep in his heart, but it gets tricky. Finally having friends, he never wants to be alone again, but it is also true he now wants to disappear from the world, his power ends up granting both and locks away the Academy and everyone in it away from the rest of the world. The final boss of the game, as strange as it is, ends up being Vayne himself, and the massive power he wields as a Mana.
Now, it was very important you get all those small story details prior to this moment before understanding why this narrative hits so hard. To use a bit of a contrasting example, I'll discuss Persona 3.
Persona 3 is a very dark game and is obvious from the outset. Yes, people die in that game, but it's a game that would be shocking if no one died by the end of it. It's not to say the deaths aren't impactful, they definitely are, but they feel very at place in Persona 3.
Mana Khemia started out as a sort of feel-good story with some fun characters, intrigue, and very much a coming of age type story with Vayne. When you get the build-up to that final battle, and the build-up is fantastic, the weight of what happening hits so much harder. Death and depression were not things the players, either the one playing the game or in the narrative, were ready to deal with. You weren't going through the plot wondering 'Oh I wonder what tragic backstory this guy had' or 'I wonder if someone is going to die' you were dealing with pretty local and mundane issues compared to that.
All those non-sad and seemingly unrelated things I brought up about the game being a lot more light-hearted, and a fun tale of a boy coming of age, they are what makes this ending hit more than anything else. It helps that I really like the characters, but the more mundane set up has so much potential for a hard hit like this game delivers.