apache 2.2 + mod_pagespeed + varnish
Have yet to test it out. I do know that domain specific code CAN be better in comparison to a generalized tool like mod_pagespeed; but I would imagine it would take a lot of effort to beat mod_pagespeed. mod_pagespeed should bring an improvement in comparison to drupal's core aggregation; you will get CSS &amp; JS Compression among some other nice things.

In Drupal land we are working on improving the page load time. Here are some projects for that.


http://drupal.org/project/wpo
http://drupal.org/project/bundlecache
http://drupal.org/project/advagg
http://drupal.org/project/css_emimage
http://drupal.org/project/imageapi_optimize
http://drupal.org/project/closure_compiler
http://drupal.org/project/cdn


Long story short: Use mod_pagespeed today; checkout some of these projects in the future.