Drupal 7 + HTTPS + Nginx + Varnish + Apache + Boost + APC + Securepages + Drupal
If you happen to develop large sites in Drupal, you might fall upon a case like this one, where different servers (namely at least one reverse proxy and one web server) interact, causing a series of chain reactions every time you change something.
It might be frustrating, at times, to try and boost a coordinated system like this, and end up getting your users frustrated because part of it doen't work, when the rest (the part that *does* work) is super-fast.