The 3D looks a bit stiff, but I do like the low-poly models. You'd probably have to do a lot of facial animation rigging to make it more expressive. Building 3D models will probably be time consuming as well as doing the lighting, rendering, etc., but I guess that all depends on what you are trying to go for. If you wanted to mix 2D and 3D, Blender can also do non-photorealistic rendering -- it can auto-outline 3D models and do toon shading -- it wouldn't be perfect though, but I've seen some folks try to emulate an anime look fairly decently.
I use 3D sometimes to help me get perspective correct or do various foreshortened scenes, but my work is all 2D drawings (done digitally).