Sophitia's ending in Soulcalibur IV. Despite the initial Narm, Algol's words to her conveys his sadness over being forced to kill his own son.
Algol: "Time is cruel. Even with all of this power, I cannot undo the past..."
Sophitia's whole motive since SCII has also been to protect her very young children. Becomes Harsher in Hindsight in SCV.
Parts of Tira's ending somehow make the psychotic, bloodthirsty, Magnificent Bitch... into The Woobie. It's just so sad and pathetic, as she's begging Nightmare not to leave her alone...
Considering how Tira always sought companionship, it's even sadder. After her time as a member of the Bird of Passage, she was more or less adopted into a family for a short period—but her insanity caused her to Kill Them All when she got into a small squabble with them.
Lizardman's backstory in Soulcalibur III is heartbreaking when you discover that he is a man stuck as a reptilian killing machine who can't speak, forsaken by everyone, even by his god, and desperately (and vainly) trying to get his humanity back while his monster side engulfs him more and more.