If you have a mod that includes a gfx folder of any description, picking up the spider mod item will cause the game to crash when encountering enemies.

I have tested this, and this occurs even when you add a empty gfx folder. I have also tested this on a few mods on the site as well. More people should know about this and it should be added to the help page on the modding of Isaac. So... uh, don't pick up spider mod if you are using a graphical mod(on mac). It's kind of ironic.