I just sent a new note to the Flocknote Development list about making Flocknote speedier. Flocknote is a very complex web application, and at the beginning of this summer, I noticed that some pages were taking more than a second to generate on our server (that's before the page would be sent to the end user!).
Investigating the performance problems using MySQL's EXPLAIN, the PHP profiler XHProf, and Drupal's Devel module, I found the culprits to be some inefficient and memory-hungry caches and some inefficient database queries. Applying a couple patches that are in development for Drupal, and adding a couple indexes on different tables more than halved average page load time.
I also am actively trying to get these patches accepted into Drupal core and the Views module. Once the patches are incorporated, millions of other Drupal websites and applications will be able to conserve memory and clock cycles as well. You could easily substitute 'Wordpress', 'Joomla', 'DotNetNuke', or any other CMS or platform for 'Drupal' here.