We have been running nginx - uWSGI, and now we are evaluating putting Varnish as a caching layer between nginx and uWSGI (similar to http://www.heroku.com/how/architecture). But, nginx only supports HTTP 1.0 on the back so it will have to create new connections with Varnish for each request. Many recommend running nginx in front of Varnish, but wouldn't it make much more sense to use something like Cherokee so that you eliminate the HTTP connection overhead since it supports HTTP 1.1 on the back?