glad to start of the discussion here. :)
Recently there has been a lot of talk about usability problems. I think the solution to this also lies in a better help system.
Drupal is not a trivial piece of software, that we can make a interface and expect the users to understand everything about it. So lets face the problem.
What about having first time tours of site. You will understand what i mean from if you go to http://cm.my.yahoo.com/ (without being signed in to yahoo), and click Yes, please! button at the top. This can be a generic feature (an extension of help module). This can be also used by other modules(like when a new module is installed, the tour will guide the user through its features). This tour can be make with transparent javascript popups, animations etc.