A client recently asked us for help with a very specific issue. The node edit page was hanging up, but only in Internet Explorer 10, and not in Firefox or Chrome. The client had WYSIWYG editor enabled.
We have mentioned before that both Pressflow 6.x and Drupal 7.x (but not core Drupal 6.x), disable page caching when a session is created for an anonymous user.
An extreme case of this happened recently, because of a perfect storm.
For sites that have lots of slow queries, disk access is often the bottleneck. For these slow queries, MySQL writes temporary tables to disk, populates them with intermediate results, then query them again for the final result.