Donncha – your comments are interesting (and rather worrying from my perspective!), but I’ve honestly noticed absolutely NO problems with Multisite Manager.
We now have 12 different ‘sites’ (with parked domains on our VPS), numerous subdomains hanging off each site and users logging on and maintaining their own blogs. Plugins seem to be happily managed via Plugin Commander on a blog-by-blog basis along with Custom Themes etc. In fact the only issue has been with the Sitewide Tags plugin!
At the moment we’re not really in a position to switch to any other method of creating sites (what with also having to think about what happens to our existing sites in the process) and as I say it all seems to work fine. Additionally I’m not sure the Domain Mapping plugin is quite robust enough yet for our clumsy hands!
But at least I know that our set up is probably not suitable for the Sitewide Tags plugin in any case.