Most python GUI APIs will be wrappers around the most common c/c++ GUI APIs. You've got a python wrapper for gtk, a python wrapper for qt, a python wrapper for .NET, etc etc.
So really it depends on what your needs are. If you are looking for the easiest way to draw native-looking widgets on Linux, Mac, and Windows, then go with wxPython (python wrapper for WX Widgets). If cross-platform isn't one of your needs though, other libraries might be more useful.
