From the mailing list, I saw a few comments about Django instances that take significantly longer to get started if they are cold. This would be noticeable if your application is rarely used.
From my application log, it looks like the first request took about 4 seconds to start.
My Django instances use 41-43 MB. Not sure about webapp2.
If you use Django-unreal as ORM, I am sure that there are several loops in the ORM translation, but I doubt that it is important. The Tastypie REST level can take from 40 to 120 ms for the same request, it seems that the performance is more dictated by this repository than anything else.