The WP_USE_MULTIPLE_DB switch controls whether MU uses numerous database SERVERS -- not databases. Of course each server does have its own databases, but the point here is that the switch doesn't divide users across many database. That is, if I understand correctly. I could be wrong....
What it appears to be used for is load balancing across multiple database servers that use replication. So in practice for example, one db server is used for reading data, and other db servers are used for writing data (blog posts, comments, etc).
Then when new info is written to a server that info is replicated to all the other servers. This is a function of MySQL Server itself.
So unless your db server is under heavy load or will be at some point then there's no need to worry about that switch.
What you DO need to worry about is too many files in a dir, etc. So the fix posted in this thread will help prevent that. Incidentally it's the same way Mediawiki software (used by Wikipedia) handles that exact same limitation - by splitting files into a large number of directories.
Anyway, someone who isn't familiar with MySQL Server replication wouldn't figure out how to use the WB_USE_MULTIPLE_DB switch... As it turns out I am familiar with that, so I took a look to see how MU uses the switch, and there's the answer.
As for worrying about your db getting too big, don't worry about it too much. MySQL is fast even with huge tables as long as your server is fast, has plenty of RAM, and MySQL is optimized properly. Worry instead about backing up your db regularly somehow in case of disk failure or corruption.
That's my advice.
If anyone out there wants to implement that switch then do a search on $db_list along with the switch name and you'll come across some wp-config.php settings that need to be put in place...