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Tear Jerker: La-Mulana
In a sense, what lay behind the Giants' civil war. Migela's faction wanted to restore the Mother to the heavens, the whole reason the Mother created them. But Sakit's faction wanted her to stay. Effectively, they didn't want to be abandoned by their creator. Essentially, it was a clash not between good and evil, but between two different understandings of filial love.
The scene after you defeat the Mother also counts, especially in the remake. The Mother lays on the ground while extending her hand towards Lemeza and cries out in anguish before succumbing to her death.
Lemeza's backstory in general. His father abandoned him as a little kid to further his career, when he grew up and got into the same field Shawn keeps poaching his research, up to and including the Treasure of Life, and if you take La-Mulana 2's known backstory into account, the rest of humanity only knows that he destroyed a world heritage site, not that he saved the species by doing so, and he's a wanted criminal. The guy just can't catch a break, can he?