It can deal with all the sites, and the plugins required by each to make them work as required. However one of the things I really hate about WordPress is that it requires MySQL as a backend, which for a site with so little content change between requests, and caching for when there is a huge increase in hits (I use WP Super Cache).
On a number of occasions I have tried to use the PDO (SQLite) plugin, however it has never worked as well as I would like; and now it seems not to have been updated since January 2010, however according to this post on the authors site, he will be looking at bringing the PDO up to date.
Now I know bma has some things to say about SQLite, but compare that with MySQL, and remember all that caching from above reduces the chance of Concurrency (and that seems to be less of an issue in V3).
Now why would I want to use SQLite? my logic is that a database is just a file some where on the file system managed by another process, If I can move that file into the location where that copy of WordPress is installed I can make backups of the state of everything in one go, as well as move the entire install +Database between computers by uploading just one zip, with out needing to do a Database Dump + Restore.
If I could, I would really like to see is WordPress with a Flat File back end, I know there is FlatPress, but its still not looking like anywhere near ready to trust, however I will have a go with it on a test machine.