My unpopular opinion is that multisite is completely unnecessary for the vast majority of installs and has major drawbacks. The only fundamental advantage of multisite is that that it saves some disk space (does that matter?). But it has fundamental downsides:

• It closely couples the database updates of many sites. (When you do a module or minor version update, you have to do the update and test on all the sites at that exact time. If you're doing it "right" it means that many sites may be offline until you're done.
• It takes your filesystem risk and instead of having one site at risk at one time, they're all at risk. So if you have a new module you're introducing or an upgrade that has a bug it unfortunately affects all sites.
• The files directory has to be managed exactly right; and it better not be sites/default/files.
  

IMO, multisite and database prefixing were for the old days before we had unlimited accounts and disk space was free.

That said, if you know exactly *why* you're doing multisite and you want to tie sites together, then that's fine. But "because Drupal does it and it seems cool" is not a good reason.

Aegir is fundamentally a multisite idea, and it deals with all these problems. It's a maturing approach to doing multisite quite well, and many people are very happy with it. That's a good reason for doing multisite, and it has all the issues above dealt with.

-Randy