Michelle Levesque is rigorously investigating a number of Python based Web application frameworks. She (presumably) has a well defined app that's being implemented in all of the systems, and is using CGI as a control. Still a work in progress, but I'm enjoying the coverage of Quixote.
I have to concur that Quixote takes some work to wrap your head around. One key lesson I learned is that every module or object must have a _q_exports attribute. A second lesson is that PTL is way cool.