Yes, I wiped all the settings. Some you can restore from a titanium backup, but be careful what you restore... apps and data ok... system data not so much. Some 2.1 settings may not be compatible with froyo.
This is what I did:
1. copy the rom zip and two radio updates on to sd card
2. Titanium batch backup all apps, data and system.
3. Boot into clockwork.
4. nandroid backup. Make sure the backup states successful before proceeding.
5. wipe all caches and dalvik
6. reboot into clockwork
7. flash the rom
8. reboot into clockwork
9. flash the radio
10. reboot into clockwork
11. flash the wimax
12. reboot into froyo
13. restore whatever apps you want to keep.
This was my first rom flash since rooting with unrevoked3 so there may be extra reboots where none are actually needed, but it doesn't hurt. You will not lose root as long as you flash the rooted rom.
If you run into a boot loop or any other issues, you should still be able to boot into clockwork and restore the nandroid backup from step 4, which would put you right back where you started from. This was my experience, ymmv.
Once you get everything setup again you can boot into clockwork and do another nandroid backup in case you ever want to go back to your freshly configured froyo install.