Mark,
upgrade is really painless. Upgrade wizard is really easy to use and does a fantastic job of moving 5.1 DB into 6.1
I do not know about 6.5, because I have not touched it yet; however, one thing that upgrade wizard CANNOT do, is fix your strategies for you. If you are using IR, I would recommend recreating them in IRD.
There are additional components that need to run in G6.1 that did not exist in G5.x, but you have already determined what you need to install, right? Beware of IVR

It is really different in G6.1.
Drop me a line if you need more help.
Vic