Just thought I'd share how I'm doing an all-AJAX site in ProcessWire: For all I know, this may actually be a bad idea, but so far it seems to be working.
I'm rendering my nav with anchor tags for hrefs, and storing the actual source URI in an HTML5 arbitrary element attribute. When the user clicks, the browser just takes it as a normal anchor, but the JavaScript pulls the actual source URI out of the link's arbitrary attribute into a jQuery .get() and displays it in the DOM. The advantage is that since this is an AJAX-only site, the user doesn't see the actual path to the content (in the status bar or browser tooltip), which could confuse them (if they were to open it in a new tab, they'd just see unformatted text).