I have used Python off and on for about 10 years and have never particularly liked it. This is funny since Ruby is my favorite programming language and Ruby and Python are very similar both in features and in the types of applications that they are best used for. For me the largest shortcoming of Python is the lack of blocks.
That said, I have two small side projects (consultingwith.me and consultingwith.us) that I wanted to host on AppEngine. I have a fair amount of experience with the Java AppEngine SDK but my gut instinct was to go with the Python SDK using the default webapp library. After spending about 5 hours writing code, I find that Python is fairly comfortable. 7/9/2011 edit: I enjoyed getting a basic system working with Python (a great learning experience) but ended up writing a feature complete version in Rails and using that for several months. In the last week or so I have re-implemented it in Java + GWT for the Appengine.