Akira/Tear Jerker

There's the death of poor Takashi, which happens right when it seems things may start getting better and as he happily goes towards Akira, calling out to him and asking if he remembers him from the past. And right when he's extending his hands to touch the kid he's so happy to see again... BANG, courtesy of Nezu. No wonder Akira has a terrible Heroic BSOD as he sees Takashi die, completely loses control of his powers, pretty much blows up the whole Tokyo by himself and, in few words, It Gets Worse.
Then there is the death of Kaori. She had zero to do with his condition. On the contrary, she loves him and genuinely cares for him despite him being a royal prick. Yet, she pays the ultimate price.
- Made even worse in the manga, where she's shot to death by Tetsuo's aide and dies in Tetsuo's arms.
When the Colonel is reintroduced in the second half of the story, one of his former soldiers recognizes him and salutes to him. The Colonel dismisses him, as he cannot help anymore. Later on, when the Colonel is battling Tetsuo's troops, one of them recognizes the Colonel as his former superior. When the other Empire soldier tells him to shoot the injured Colonel, he shoots him instead. As he's helping the Colonel escape, the latter asks him why he stayed after the disaster, instead of fleeing. The soldier's answer? Because his wife died in Neo-Tokyo. Right after that, he is shot and killed from afar by more Empire troops.