Ragnarok: the Animation has one such moment when Alice, Maya's friend, is forced to become a monster and Maya-chan kills her with her own hands before realizing who she is. The subsequent episode is a tear-jerking episode after Maya realizes what she's done and apologizes to the already dead Alice.
Jiltus' act of Taking the Bullet for Maya inflicts serious injuries to her. Despite that, she manages to use her last strength to conjure a barrier that protects Maya and Poi-Poi from Zephyr's Lord of Vermillion, which results in her death. This leaves a heartbroken Maya behind.
Keough's final farewell to Yuufa in episode 26. All of it.
This part is extremely heartbreaking:
Yuufa: Where are you going, Nii-san?
Keough: Yuufa, I can no longer be with you, from now on, stay with Roan. He will protect you... indefinitely.