You can customize materpage, page layouts (or create new), xml, css etc ... but not files containing c# code
To customize the site you just press file --> open site --> and enter the Url to the site.
My advice is NOT to user SharePoint designer. You can face deployment and performance issues. A page that has been modified by SharePoint cannot be cached. That includes all the custom caching you might be using the your custom code (HttpContent.Current.Cache).
That said I am involved in an Internet facing site that has been build almost entirely using SharePoint designer and that works and preform ok (no customer complains regarding perfomance). But deployment of new code is a hell. That site was one of the first
sites in the world to launch on MOSS 2007 and we didn't know better. We do now ...