I'll preface this by clearly stating that Zotero is absolutely indispensable; I wouldn't be nearly as organized without it. It's very important to me that such tools be open, and Mendeley in particular is a complete disaster in this regard (see their history with encrypting user data).
That being said, Zotero is very much a "least worst" tool in my opinion.
* Overly rigid in how it goes about modeling document types and metadata fields.
* Doesn't handle bookmarks, browsing history, and other various data types. At first glance it's easy to dismiss such things as out of scope, but I find that my typical workflow results in reams of such unsupported data being generated and manually tracked by me. The problem is that this unsupported data is often tightly coupled to the data I'm managing with Zotero, which is frustrating to say the least.
* An incredibly heavy and inefficient piece of software.
* It's far too difficult to set up and manage my own sync server (last time I checked, at least). I don't really want to share all my data with the developers, but it's very inconvenient not to do so.
More on topic with the broader discussion - knowledge and data management in general seems to be a largely unsolved problem, particularly in science and particularly regarding interrelations between and versioning of arbitrary pieces of data.