DNSMadeEasy has a global traffic redirector ( http://www.dnsmadeeasy.com/services/global-traffic-director/ )
That then sends a request to the closest Linode data center.
Linode instances run nginx which redirect to Varnish, and the Varnish backend is connected via VPN to the main app servers (based in the London datacenter as the vast majority of my users are in London).
I use Varnish behind nginx to additionally place a fast cache close to the edge to prevent unnecessary traffic over the VPN.
Example: USA to London traffic passes over the VPN running within Linode, and the SSL connection for an East Coast user is just going to Newark. If the requested file was for a recently requested (by some other user) static file, then the file would come from Varnish and the request would not even leave the Newark data center.