Jinchuuriki!Sakura's life in general: her own mother viewed her as a monster, and her teammates were killed in front of her by Kimimaro, leading to her totally breaking.
From that same chapter, the complete obliteration of Wave Country.
Kazama being utterly broken by Tsukiyomi revealing that most of the people he knew and saw as friends never really cared about him all that much to begin with.
N's life: When the poor guy finally found a place where people were nice to him, his departure from Konoha triggered a global war.
Sasori's Heroic Sacrifice. Even critics of the fanfic bawled when he kicked the bucket.
Jiraiya's death in Chapter 46. Made especially tragic with the memory of Naruto he sees at the end of his life. It also draws several parallels with the Sandaime's death in canon, which just makes it all the worse.
