Most people do a backup, a clean install, then restore the backup. I have done plain upgrades on ours from 4.1.2 to 5.0 to 5.5 with no problems other than a few custom templates that needed to be tweaked. Check out the Bugs page for 5.6 before you do upgrade. There seem to be a few little problems yet, VPN being the most common.
Most of the benefits of 5.6 seem to be "behind the scenes" stuff. For all the stuff we do, 5.5 and 5.6 seem to be identical feature-wise. For now, I'm sticking with 5.5.