I upgraded vBulletin to 3.5 on my site when it was officially announced. It went very well. I made a file containing all of my changes that would have to be redone, did the upgrade, then applied my changes. I worked on it for a couple of hours or so altogether, but the site was only down during the upgrade itself which was probably about 30 minutes.

In my opinion, there isn't anything major that the users will see different. There is so much more that could be done, but it doesn't look like vBulletin is going to get a major upgrade very soon.