Tweener starts with Seth asking for Michael to help him. While Michael is clearly disturbed, he chooses not to do anything because T-Bag is now part of the group, and walks away from Seth when he asks for help again. A short time later, Michael is horrified when Seth commits suicide and blames himself for not doing something in order to not make waves, and says that his and Linc's mother would roll over in her grave if she knew he hadn't helped someone when he could. Harsher in Hindsight when you learn the truth about their mother...
You know Linc isn't actually going to get the chair in The Rat, but it's still incredibly sad to watch him make the goodbyes to his loved ones, and watch Michael try to come up with just one more thing to save him.
Westmoreland's death. He only joins the escape attempt because his daughter is dying and he wants to see her again, he receives his fatal injury while making sure that the route they're going to use to escape isn't exposed, and he doesn't even get to see his daughter again.
Michael's "You used me, Linc" — after Burrows tells him that Sara has been long dead, but decided not to tell Scofield not to distract him from fulfilling the escape plan in order to save LJ. The entire conversation is already painful, but just the exhaustion and sadness in the former's voice really gets to the heartstrings.
Michael's death at the end of Season 4. Made Hilarious in Hindsight by fans who claimed to have cried for days after his death only for Season 5 to come along years later and reveal that he was really just Faking the Dead.
The chronologically-last scene of Season 4, when everyone gathers for Michael's memorial.
