Pywin32 to call native apis for GUIs sounds very, very painful. I had a few run-ins with pywin32 and COM automation, I don’t think I could bear the thought of developing a full UI with that sort of hacks. At that point, might as well go C# (or IronPython, if it’s still around) and enjoy the VS goodies.
COM might have its issues, but I meant using the win32gui, win32api etc. modules to call the native win32 C API for UI. That's hardly a hack, and perhaps even slightly less painful than doing it from C. (I'm only using it for some fairly small things, though.)