The problem isn't "will the upgrade to Lion cause problems?" but rather "getting a new OS is an occasion to clean your computer, should I take advantage of that opportunity?".
I've never clean installed my Mac for 3 years, and I'm not sure if it's running slower than it used to, as I can't remember what it was like 3 years ago.
However, I know that in Windows you do a clean install every year or so, and the difference is noticeable, mostly because it removes all the useless processes that start when you log in. On a Mac you can easily keep track of apps that start on login, though, so this might not be an issue.
Another thing is: what if you have corrupted fonts, corrupted app preferences and whatnot? Maybe they're making your system slightly slower but you'd never find what's doing this, mostly because it's not a single thing and it's not noticeable enough. Now a clean install would remove those corrupted files...
But then you'd probably end up copying your fonts back, thus copying the corrupted ones back again... or maybe they weren't corrupted in the first place, but got corrupted during normal usage? That was the case with an OS X update lately, but it was later fixed in yet another update.
Also, I just found 4GB of Cache files in my user Library... Those cache files were from Bridge CS4, that I have removed from my computer 2 years ago. So when you use the official uninstaller for Adobe apps, they STILL leave cache behind, and huge amounts of it. If I would not have noticed, then a clean install would have solved this problem. Maybe there are more cache files around, I just don't know about them...
Also, some apps just have problems, for no specific reason, and you live with it. Some apps give you an error message and you don't really know why. Who knows, maybe it's a corrupted file that would not get fixed unless you did a clean install.
By "clean install" I mean Format > Install Lion > Install every app one by one from the original installer > Copy back every single file one by one from a hard drive. Formatting, then restoring from Time Machine won't do a thing. It will copy back your corrupted fonts the same way.
A true clean install is extremely time consuming, as it requires you to remember all the plugins, settings, preference panes, apps, extensions, and all the tricks you did to get things work when there was no official support. Doing all these can take days and days of frustration, and by the end of it you will probably wish you had just upgraded.
Computers today are extremely complex and your data is the way you want it, customized like hell. I think that unless you have specific, unsolvable problems, then just do an upgrade.
I switched from Windows because I hated that you install your OS, lose all your data, and a year later you can start over again... It's never over. Hopefully (and apparently) OS X doesn't require this.
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