We had a lot of issues when we tried Varnish. New posts were caching oddly. After you posted, you would see your new post, but no one else would. Refresh and it would be gone for you too and took 5-15 minutes for anyone to see it again after. Personally for me, I like Memcache over APC, each site on the server can have it's own cache with Memcache, just run each instance on a different port. APC is a good choice too, many of our customers use it, just a personal choice for me to go Memcache. Google Mod_pagespeed I installed on my test box today but haven't had time to test it yet.