Kenji's death and Kenshin's subsequent helpless denial.
And then he feels the real impact a couple weeks later, when he's captured and drugged by KaibaCorp, and he breaks down with Aoshi because he "only wanted Kenji-chan's sword, why won't they let me have his sword...?"
Elderly Saitou dies alone because the other two are out trying to fight fate to keep him alive, and he wishes privately that they would come back and just be with him. He sits up for his final few nights waiting for them, but smiles at his own foolishness because he knows they're not coming.
Rei comes home from his vacation to an empty house, and goes about his business believing everything is normal, only to find out when his phone charges that his parents were killed three days earlier...