The Facebook design has zero familiarity to it. I have been using the site for over 5 years now, at least once a week, and yet I have zero familiarity with the product. When I click on a link in Facebook, I have no idea what is really going to happen. I have written blog posts and popular guides on Facebook yet when I am helping others secure their accounts I find myself just clicking and guessing. It would definitely be in the top 5 products that I have used in the last 5 years yet it is the only popular product that I can't navigate blindly.
The menu's are starting to remind me of the toolbar hell of later Microsoft Office versions (a reason why a lot of power users are hesitant to upgrade Office).
I think Facebook really need to streamline their design, separate brands from real friends in the news feed and sit down and work out how they can expose deeper functionality of the platform to users without just throwing dozens of links into the interface. When you have personal pictures from friends mixed in with brand messages users are more likely to feel that their privacy is being violated.
Edit: to add, this is why I think Facebook isn't as secure in popularity as many analysts would have you believe. Pinterest is an example of a real threat to Facebook - a site that was designed with social and e-commerce ingrained in the product with an easy to use interface. That is a billion-dollar opportunity to Facebook is about to miss out on.
Edit 2: My attempt to shop on Facebook:
https://img.skitch.com/20120219-nd4peencu2b7kf9534juhb1ytc.j...
vs my attempt on Pinterest:
https://img.skitch.com/20120219-fjyq53h693eb4fnfitamgsmuc5.j...