Having developed a smallish site with GAE, I have some thoughts
If you mean "huge" like "the next YouTube", then GAE might be a great fit, because of the previously mentioned scaling.
If you mean "huge" like "massively complex, with a whole slew of screens, models, and features", then GAE might not be a good fit. Things like unit testing are hard on GAE, and there's not a built-in structure for your app that you'd get with something like (famously) (Ruby on) Rails, or (Python powered) Turbogears.
ie: there is no staging environment: just your development copy of the system and production. This may or may not be a bad thing, depending on your situation.
Additionally, it depends on the other Python modules you intend to pull in: some Python modules just don't run on GAE (because you can't talk to hardware, or because there are just too many files in the package).
Hope this helps