Granted we don't have a need for SSL and not being able to use C libraries in python has caused us many hours "pain", but compared to the alternative for a small company like we have, it's well worth it.
My biggest issue with AppEngine is that there's no full-text index functionality, and there's no way to create your own. We've tried everything, and nothing works if you have millions of documents like we have. Our search is still external to AppEngine but we're hoping that Google will do something about it sooner or later.
Certainly ironic for a Google platform to be so bad at search.