Excellent list, RvR - I highly recommend one of the resources cited, https://elgg.org/discussion/view/310368/recommendations-for-a-medium-to-large-elgg-site. The MySQL section describes problems with table-level locking on a MyISAM engine, definitely something that we suffered from.

Switching to innodb has pretty large gains, separating the database from the file server, and offloading search to SOLR (or some other dedicated search app) is huge.  Search is the slowest queries of anything contained in default Elgg, it's why I've spent so much time building the elgg_solr plugin, we use it in ~80% of our projects.

Thanks for the resources and the replies everyone, this will be a great starting point for us.