There's a lot of detail at the low level that you miss by using any layers of abstraction (on both Python and Java platforms). That detail is important for getting maximum performance out of your application and correctly dealing with AppEngine's unique transaction model.
The choice of web frameworks is tougher. Startup time is important right now for AppEngine (although slightly less important with some of the new features rolling down). You'll want to use the lightest-weight framework you can find.
On Python, I've had great luck with webapp + Django templates + raw Datastore APIs.
On Java, Guice + Guice servlets + raw Datastore API is really lightweight and fast. We've also developed our own Django-like templating system for Java that we hope to open-source at some point.
Anyone else with more GAE/Python experience want to chime in?