I'm using a single wordpress installation for a several sites. For each site
/usr/share/wordpress is simlinked into /var/www/domain.name ,
upload_path is set to /srv/www/wp-uploads/domain.name and
upload_url_path is set to http://domain.name/wp-uploads .
WordPress MU isn't needed, because the sites are completely separated (except shared wordpress's sources). I prefer this configuration, because it works fine with XCache (php-files cached ony once) and it's easy to maintain (Debian's patched wordpress package even have a special utils for it).
It would be great if you allow nextgen-gallery to store images outside a wordpress's root (in a folders like /srv/www/wp-gallery/domain.name) and allow users to set a custom (independent from gallerypath) url for images (something like http://domain.name/wp-gallery) analogously to WordPress 2.5' upload_path and upload_url_path.