I've been using wxPython for about 6 months now, and I'm pretty happy with it. It has it's fair share of quirks to get used to, but then all powerful, cross-platfrom gui toolkits do. It's got a lot of really powerful widgets (there's one that renders simple html, there's one that wraps Scintilla, there's one that let's you use OpenGL, etc).

One really cool thing about it is it comes with a demo app that shows how to do almost anything -- how to use the widgets, how to use threads, how to handle events, etc.. It's basically a big collection of small programs. You can see the code in one tab and see the program in action in another tab. Here's a couple screenshots:

http://crookedgames.com/wx_python_demo_action.png

http://crookedgames.com/wx_python_demo_code.png

Yet another cool thing about it is Robin Dunn, its maintainer. He seems to go through the mailing list every day or two, and answers most questions that people have. He's been maintaining the project for a long time and knows what's up. Maybe I shouldn't be advertising him as tech support, but I've received helpful assistance from him more than once :)

Since writing this I've moved from wx to qt. I much prefer qt. It's faster, less buggy, and better documented. PyQt is definitely the way to go.

Just a note in case someone finds this via Google or whatever.

If you go the wxPython route, then there is wxGlade to make designing the interface easier. http://wxglade.sourceforge.net/