MS Office lost me when they rolled out the "ribbon" UI. I never understood it, and still have to hunt around for ten minutes any time I want to do something that's not visible.
Granted, this is because I've never been much of an Office user. But over the years I came to know where pretty much all the features were in the "classic" Office menus. When MS threw that out and put in a radically different UI, I decided that my minimal word processing needs did not justify the pain of re-learning the app.
As of Office 2010 the Ribbon has improved a lot more. It's still annoying, but it has really grown on me over the past few years. Another nice feature of 2010 is the addition of formatting options to the context menu, so you can easily change basic text and image formatting by right-clicking them instead of flipping through the Ribbon.