Minor, but in Fun Science: Sound, there's a character called "Mr. Information," who talked and acted like one of those videos they show you in school that talks down to people's intelligence. Charlie punches him in the face. Anyone who's ever watched a video with a host like Mr. Information can only dream of doing that.
Terminating his friendship with Alex Day after the latter was revealed to have committed sexual harassment. Even if it was the right thing, breaking off a friendship that's lasted so long is seriously hard.