- Donna getting fired. The look on her face is just heartbreaking. Even though we know she'll end up coming back one way or another, it's still heartbreaking.
- Mike's grandma dying. His face when Rachel tells him is just devastating. Doubly so because he was finally making enough money to be able to properly take care of her and had just bought her an apartment when Rachel comes to see him.
- Louis's cat dying. Anyone who has or had a cat will understand why he looks like his world has crashed.
- In Season 3, when Louis tries to befriend Mike, after Harvey had been an unforgiving jerk to him since the season 2 finale, with Harvey's blessing. By the episode's end, Harvey forgives Mike and Mike goes back to Harvey at the first opportunity... after he just told Louis he would join him. You can just see Louis's heart breaking as he walks up holding a cake, which he ends up throwing away. It had "Welcome to Team Litt" written on it. Sniffle.
- Season 4 does another to Louis. To be the hero, he had to break the law. The law comes biting back and the only way to save himself would be to frame Harvey. While Louis can be slimy, he's not that slimy yet of course going to prison for a fairly significant felony and destroying his life is obviously not the most thrilling option either.