I use Drupal for most of my sites. I use it in many different ways and it has been working real good for me.
On one of the sites, I use the ThemeKey module to select a different theme once you are logged in. This means, when I want to switch themes, that one theme selected for logged in users sticks, whether you disable it or not, it remains selected by the system.
Well... one thing sticks from themes, their .info file. You just cannot refresh the cache properly unless you disable the theme, then re-enable it. (By the way, when disabled, don't go to the Blocks administration screen ...