Well, your question is kind of broad, but I'll take a stab at it. First off, there shouldn't be any need to "start over" on your site. The beauty of a CMS like mojoPortal is that the pages are all rendered on demand, so changing the look is as simple as putting a new skin folder under /Data/Sites/[Sitenum]/Skins, and selecting it under Administration, Site Settings.
So what you need to do is convert your design into a mojoPortal skin. You can do this either with the "classic" method (using a delivered mojoPortal skin for reference, and the Firebug plugin for Firefox, convert your design's HTML file into a layout.master file, and integrate any mojoPortal-specific CSS selectors and other support files to the skin); or you can use Artisteer to recreate your design, then export from there and turn it into a mojoPortal skin. From experience I can tell you that the first method may be a bit tedious and frustrating, but you'll gain a very good understanding of the nuances of skinning, and how CSS is used within mojoPortal. That said, after I'd created a couple of sites using the "old" method, Joe added Artisteer support to mojoPortal, and we haven't looked back since.
Whichever method you choose, the skinning documentation is pretty comprehensive, and we'll try to help you out here on the forums if you get stuck.
I'm looking forward to seeing your design running on mojoPortal!