General speed/performance on large Craft build
We are constantly seeing the deleting stale template cache timeout problem on our servers - try increasing the time PHP can execute for to something very long. It seems like clearing the caches counts as one PHP request and not a bunch of tasks, so they can time out.

Good use of cache tags helps, and caching globally can also help - but other than that all I've found to make complex Craft builds faster is using something like Varnish or nginx. Neither of which are simple and both of which I've avoided so far.

PHP7 will help a lot, but I'm not aware of any distro that has PHP7 available yet.