The best way to experience the "how would start from scratch be" without starting from scratch is to create a new empty user, remove all "login items" and work from there. That's as close as you can get. Of course there are other factors that you might have installed and might be slowing down your system (old extensions, drivers, etc that may be logging in excess, faulty services, etc.).
If you do perform a clean install (and have a backup on another drive), "manually" migrating is not that bad. You will have to:
Drag your apps from Old_Drive to the New_Drive (a good opportunity to not drag those old things you don't use anymore) :)
Before starting them up, find ~/Library and migrate Preferences and Application Support for the apps you want to conserve (tho sometimes trashing the preferences is a good fresh start).
Also check /Library/Application Preferences and all the libraries in general.
Copy over your Documents, Music, Pictures, Movies, etc. (Another great time to leave old stuff behind).
Reconfigure your new computer too, network, your dock, the finder settings you had, your wallpaper, etc. All that stuff.
In regards to your specific question, it's "half correct" in my experience. I upgraded from 10.3->10.4->10.5 but then Snow Leopard reappeared, tho I was going to Upgrade, my drive crashed and I decided it was a good time to start again. I had backups but didn't feel like migrating (because Migration assistance won't let you pick individual applications it's an all or nothing) and I had old copies of Photoshop and stuff that I didn't want behind.
Also the Differences between "Snow Leopard" were "huge" in terms of underlying OS, so It looked like a good idea.
It's a pain the first two days, but then you quickly begin to get things back and, to quote the movie The Abyss: "the body will remember". ;)
Another thing that may or may not be annoying, depending upon your software, is that you'll have to re-register some apps but you have 1Password with all your licences, don't you? :)
Finally, you shouldn't do this without having a backup (bootable clone) of your current drive, JUST IN CASE. A Time Machine is "ok" but I wouldn't only trust that as the recovery process is much slower than a simple boot the new drive :) So if you have a cloned drive, you can always reinstall and see for yourself, if you don't like it, clone your drive back.
P.S.: To directly answer your concerns: You shouldn't get much trouble with permissions, nothing you can't really "force" and fix and preferences… well… all of them until you start copying stuff back! :)