Ongoing Drupal Issues
dodgy database prefixing
To use the database prefix stuff, you set a prefix in your settings.php but er, you then need to manually modify the database creation script yourself. It seems as you might fear that then you will have issues with a those modules which are not prefix aware. Also you need to be careful with sequences and other stuff. Looks like this pretty basic feature is not ready for primetime. This guy has posted a script to create the tabes at least.
If you run drupal in a subdir, and want clean URLs, you need to set RewriteBase in .htaccess. I guess this means other sites not using a subdir will then not have clean URLs but you could put the rules in the vhost in httpd.conf instead.