Because she's a cartoon stereotype of a mad scientist, she ruins every joke by just mugging to the camera and constantly overacting and even when she's in a scene and she's not the focus, she still ruins those scenes because she's doing "whacky" shit in the background.
I find myself in the odd position of actually liking 3 of the 4 Ghostbusters in this movie, when I went in thinking I wouldn't like them at all, but McKinnon just ruined it for me, too much overacting. I would place most of the blame on the director though, because if thats what she's normally like, the director should have reined her in, instead he gave her free reign and she ends up ruining it.