When I was putting together my Carthage True20 game, the idea was that all the weird monsters of D&D and mythology were real, but they had been all created by alien experiments and people had come up with all the stories of the gods and godesses to explain it. (Derivative? Yes. Stargate? A little.) So in that context, having a ton of anthropormorphic races made sense. Aliens would combine bull and humans, humans and horses, while trying to create the perfect servitor race. (At least, my aliens would. Your aliens can do whatever they want. I'm not the alien police.)
From a more purely fantasy game standpoint, hybrids still work for me. When you have creatures that can take human form (like dragons and ogre magi), and humans who can take the forms of animals and monsters (wild shaped, shapechanged or polymorphed), who's to say what the effects might be? My rule on these hypotheticals is this: I side with whatever is most dramatically appropriate/the most interesting. That's the benefit imagination has over reason.