ergophobe - 4:45 pm on Aug 17, 2011 (gmt 0)
The one downside I've had with drupal multisites is when modules and themes get updated at different rates, so if you have a core update and some modules are incompatible, you are stuck.
If you use the same modules on all sites, no problem - you're stuck no matter what. But if you have 4 simple sites and one that is all tricked out with a complex theme and a zillion plugins, your update may be held back for all sites while you wait for compatible plugins for the one site.
If the sites are all rather similar and start with the same base theme and similar sets of plugins, no problem.