For me one of the best features of Varnish is ESI (Edge Side Includes). It allows you to combine elements with different lifetimes into a single page. This way you don't need to regenerate a complete page as soon as a news listing somewhere on the page changes. And you can still cache pages while displaying user-specific information somewhere on the page. This lowers the load on your application even further and it can also help in simplifying your application, by focussing purely on the content of the page and loading all other elements via ESI.
He talks about the upsides and downsides to using the technique and what to avoid when implementing it in your Varnish config. One solution to the problem is sending an ESI "marker" to tell Varnish that a certain bit of content needs to be updated. He shows how to put it to use with a Zend Framework view helper that adds a special "esi" tag to the page when the content for a URL needs to be updated.