I notice that when setting up a network sites we currently have 2 choices, subdir and subdomain.
I'd like to see a 3rd choice - domain.
I have a handful of wp blogs I host for friends/family. These folks all have their own "vanity" domains that I've registered for them. I do this on a FreeBSD box that runs apache, with virtual named hosts (so a single IP hosts all of the vanity domains). I have installed 3.0-alpha on the (virtual) site http://wpmaster.my.site .
I have selected "subdomain" as the network site choice for each of the sites I host, which means when I add 'foo.com' as a subdomain site, it gets set up as foo.com.wpmaster.my.site, so I have to go thru and correct the URLs for it in the config. Not a huge deal, but it would be "friendlier" if I didn't have to do it at all.
Finally, while the "Upload Path" is already correctly handled, I have to figure out what to do about the "File upload URL". I figure something could be done about this as well.