* No clue about namespacing. If you pick the wrong name for something, you can have name clashes within a protobuf, across uninterpreted option classes, with protobuf source code, with your own source code; and it's different if you're in Python or C. Nowhere are naming restrictions defined.

* The API is maddening and inconsistent, especially in Python. (It's totally different between Python and C.) Some things look like lists but really aren't (e.g. you can't assign a list to a repeated field in Python). Even basic reflection (e.g. to get at uninterpreted options) is a Lovecraftian nightmare, and the docs are wholly unhelpful.

* Good luck serializing a list. There's not really such a thing, despite that the API pretends like there is; there are only repeated fields. So you need a separate flag to distinguish "empty list" from "not present list".

* Abstruse implementation. There are so many layers of indirection in the generated source and the core library that I wouldn't know where to start debugging.

Not sure if they fixed any of these issues with proto3.