What makes a speaker too big for a given room?

Stanwal is correct regarding the distance between drivers requiring a farther listening position to get a proper blend of the drivers. Dunlavy speakers (SC-IV and larger models) are a good example. Another consideration is low frequency response and whether the room will allow bass to develop properly.

A very large cabinet can become a problem in itself if the room is too small to distance the speakers far enough from each other. They can have huge reflective surfaces (Dunlavys come to mind again) that can mess with your soundstage and imaging. However, this can be remedied with treatment between the speakers.