I can't tell you the stress and annoyance I've had from trying to upgrade large wpmu sites using the Site-Admin>Upgrade ap.
The number of times it crashes the site, calls teh database to a creaking halt or just sits there is painful :(
I've tried no end of configurations - from locking everyone out of the site while upgrading to twaking sql settings but no joy has been had.
I reckon the the upgrade script is too full-on - it need to have a 'gentle' upgrade option or come with instructions on how you can run it on a site with over 10K blogs without killing everything.
The same goes for the sk2 upgrade script - it's great but I'm spending the whole day watching for sites falling over.
Any ideas?