After some thought, I've come to the conclusion that Drupal's most significant usability problem is findability. Findability[1] is defined as:

a. The quality of being locatable or navigable. b. The degree to which a particular object is easy to discover or locate. c. The degree to which a system or environment supports navigation and retrieval.

The true seriousness of drupal's findability problem may not be immediately evident to expert drupal users. In addition, in various usability surveys, and studies, there is no immediate evidence of Drupal's findability problem.

"A modern paradox is that it’s simpler to create complex interfaces because it’s so complex to simplify them." -- Pär Almqvist , Fragments (of Time)