Mike's grandma dying. His face when Rachel tells him is just devastating.
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.