Does Cython give you much better results than PyPy? I would have thought that if just a few type annotations make a big difference tracing in PyPy could figure them out.
I don't know. We're using a bunch of C extensions that aren't trivially compatible with PyPy, so using it isn't really an option -- which is a pity, since PyPy sounds pretty amazing. Cython, on the other hand, integrates really well with CPython, and it can be as fast as C if you need it to be. I'm pretty happy with it.