This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Oyasumi Punpun
When it was revealed that Punpun's mother was the one sending the letters to Punpun.
While talking with Sachi, Papa Punyama recalls how Punpun used to be, and also the time when his son and his childhood friend Harumi went to look for falling stars, which ended with Harumi getting hit by a motorcycle. Poignant not just because it's interspersed with scenes of Punpun attacking the guy from the convenience store that criticized Sachi's manga, but because you get to see how much Punyama regrets his failures as a parent.
Chapter 138 concludes with Aiko kissing Punpun before recalling aloud the shooting stars and beautiful night sky she and Punpun saw that night and they both fall asleep, exhausted. In chapter 139, Punpun discovers Aiko's lifeless body hanging from a rope later and as he laments the choices he's made, carries her on his back, wondering what kind of life they could've had together had they grown up the normal way.
Sachi finding Punpun after his suicide attempt.
Sachi walking out of Punpun's hospital room, thinking that once he gets better everything will be okay again. Then the police show up...
"Who are you?" "I am your friend."
Chapter 145. All of it.
Punpun waving goodbye to Harumi in the last chapter. Even worse is that Harumi doesn't recall his name.
Made worse when you remember the story that Papayun's dad tells about how he felt about Harumi and depressed it made Punpun and how that incident shaped his life.