You will have to factory reset as part of the deal. Even between Sense versions, the differences are apparently non-trivial. That is why I suggest the backup for your "Best Sense Rom" and "Best AOSP Rom" at least. Despite any decision you make, you will eventually want to try to see if the grass is greener on the other side and switch. With CM (or AOKP, etc) you can easily just restore your backup and flash the latest version on top with no fuss. Not so with Sense stuff, you need to reset not only between each ROM even if derived from the same original source... but you will often have to do so on the same ROM between versions. Which is where you will end up flashing, getting a first impression and either sticking with it or restoring a backup of one you like.
CM does still have some issues that get me to bounce back to Sense sometimes. The camera is not as good. The 4.2 Camera is closer, but Sense is known for a good Camera, so that is not a big surprise. Apparently new model Toyotas without the Nav option do not like Pandora over bluetooth... that is the most annoying for me, as well as currently there is issues with Nav crashing. The best part of butter is still not working yet, and I hope that my graphical issues get resolved when it does get turned on. It is still noticeably faster than Sense though, and the multitasking is great.
I recently tried the Venom Sense ROM, and after recovering from settings overload, am putting in a little time to get it setup to make as my Sense ROM. I had been using CleanROM dev 4.5 for that, but the new Sense is a little quicker, and I was having a couple issues that were only going to get solved with a factory reset... I didnt want to put in the time on an old build. I had been trying to wait for JB, but oh well.