Heh, only 25..250 X to go. We did a direct line for line translation of some numerically intensive code from Python to C++ and saw a literal 1000X speedup. On other projects, it's been more like 100X slower. That says two things: first Python can be really slow, second, for some programs, Python doesn't really save on lines of code over modern C++.
I've been very impressed with PyPy however. In testing, it can sometimes sneak up to less than a factor of 2 slower than C. However, the bummer comes when it doesn't hit that mark and you have no idea how to trick the JIT to do better. If it works, great. If it doesn't, you don't have much insight into why.
Finally, I've always been able to get Cython to parity with C++. However, when I'm done, I wonder what I gained. The C++ isn't that much more complicated than adequately type annotated Cython.