I have found that the worst (but not the only) cuplrit is the Visualization Toolbar - you know, the one that has Fit All In and Rendering Style. This toolbar is very prone to pushing everything left of it further to the left every time you restart CATIA. When I undocked that toolbar, the rest of them seem to stay in place a lot better.
Also, on the Reference Settings will take multiple paths. The first path is the overriding path, with the second one only fixing those things that the first doesn't lock or specify, etc. Setting your "safe" settings to the second folder, and then write protecting it, should help you when you go to delete your base settings. I believe (but can't verify right now) that the User Settings work similary.
I'm with Eric, when we have as many users as we do (~2000), then I never trust what the user has set up. There are just too many settings and too many users - I can't keep up with it all. We have provided them with a utility that will delete their settings whenever they want.