thought i would post some feedback here to describe my results of trying to use cloudfront with custom origin
firstly i had to use w3-total cache in mirror mode as there is no longer any need to upload files to s3, this worked perfectly
as i expected to be the case, using W3TC in mirror mode with cloudfront doesnt gzip content served from cloudfront, i'm guessing here that w3tc is going to need a cloudfront mirror mode which also generates gzip versions of js and css (and txt based) files and updates relevant urls during the rewrite phase.
cloudfront doesnt read query strings (eg file.css?20101112)
this means if you use things like thesis and its css editor or even if you update plugins (and serve there files from cdn), you will have to invalidate the relevant files on the cdn manually if you make edits or updates to files that would get served from the cdn
otherwise, it seems to me like it works well with cloudfront as with any other OP cdn