I recently upgraded from 2.9 to 3.0-beta and initialized BuddyPress. I also enabled multisite (where my users could sign up for a blog).
I've noticed the following problems:
1. Posts that had attachments that weren't either attachment page links or links to the image themselves have had their link structure changed. Instead of trying to get the image from /wp-content/uploads/... it tries to get the image from /files/.
When I created a directory called "files" and then dropped in the folder structure as it appears in the link, I get a "404 -- file not found" (even though I'm staring directly at it in my FTP browser...)