I've been working on a config for a CMS that's about to get pounded in the next couple of months - here's what it does:
1. Everything that flows through Varnish has a 5 minute TTL set - keep the origin server lightly loaded.
2. If Varnish can't get to the origin server, there's an hour to get it right - a "grace" period. That's pretty much an eternity in web years so it should be OK.
3. If the client requests the CMS, redirect to the proper backend server.
Other than that, it's pretty simple - handles POST requests by passing them back to the origin server and makes everything else nice and fast.