The original use case of the Multisite feature in WordPress (formerly WPMU) was wordpress.com, where users can create and manage their own blogs, independent from all the other blogs in the network.
Outside of wordpress.com, this is the more common story: someone sets up a multisite installation and needs to create and manage several sites, usually with similar appearance and functionality, but different enough to warrant distinct child themes.
In this later scenario is where the administration interface falls short. This is what needs to be streamlined in order to make Multisite as user-friendly as all the rest of WordPress.
I’ve found myself writing several plugins for this use case already:
Update: Ipstenu posted some common scenarios when multisite should not be used.