Its safe to assume that a typical skin would be compatiable with 5.x. There appears to be many new features added to the skin engine and the skin engine has become more of a module object then its original skin only engine, which is good. You can package skin objects with skins now. :)
the only differences you are likely to see are how the nav menu is rendered, and possibly some spacing issues which need reworked, as I believe 5.x DNN is suppost to be a bit more XHTML compliant.
Which could mean it uses a few different tags here and there which might create some spacing issues. Nothing that wouldn't be quickly fixed though.