I often come to PyPI to find out "what's new in Python," but it can be frustrating reading through the list because so many packages are of interest only to those already committed to specific frameworks, especially Zope/Plone and Django. A better UI would let me filter out packages by category--or at least exclude ones that contain specific words. This is now a common capability in AJAX table interfaces.
I would just click the "Browse all packages" link and keep reading, but it doesn't actually lead to a page that lets me browse further back in time. It takes me to a page with 178 different categories I'd need to dive into. Or I can "List all packages" which, quite literally, lists all packages in alpha order, with no categorization, alternate ordering, or filtering at all. Those substitute alternate overloads for framework overload.
In short, PyPI would benefit from an interface update. IMHO, of course.