Currently, I have a test multi-site WordPress server set up with Cloudfront and no S3.
Tested ec2 domain and the site comes up fine. No issues.
Added the domain mapping plugin, added a subsite and the subsite domain works fine, but the primary blog domain does not work well. I can see the frontpage using the blog domain, but the links are pointed to the ec2 domain. I can however, manually replace the URL with the primary blog domain and the page/post will come up. Summary:
wp_options -> siteurl is set to http://myprimaryblog.org
wp_options -> home is set to http://ec2-...compute-1.amazonaws.com
wp_site -> 1 is set to http://ec2-...compute-1.amazonaws.com with path set to /
wp_blogs -> 1 is set to ec2-...compute-1.amazonaws.com with path set to /
wp_blogs -> 2 is set to ec2-...compute-1.amazonaws.com with path set to /secondaryblog/