Upgrading CMS Builder from Version 2.08 to Version 2.61+
Did something similar recently and it worked well in a single step with one exception. Somewhere between these two versions the CMS started to salt and hash the passwords in the user accounts table (and secondary membership table if you use that). There was a problem with users no longer able to to log in. Manual correction of the passwords was required in one case for us. On another project, we had to get the folks at Interactive Tools to trigger an encoding pass on all the member account passwords. Fine after that.
The only other item we run into is more common. When the MCE editor script gets updated, some users need to clear their browser cache and relaunch or the WYSIWYG editors don't show up. Minor.