You can store the /Users folder on any disk provided it is mountable at login (clearly that should be the case with another partition on the boot disk). I think it's best to setup an admin in the default location and then set your own user account to be on the second partition via the 'Advanced user settings' (right click the User in Users & groups to set the home path).
It doesn't really simplify a 'clean install' because you cannot totally erase the HD, you can only erase the filesystem on the boot partition. If you plan on trying things that alter the disk (like installing Linux/ Windows, or using risky *nix tools like dd etc 🙂) your idea doesn't help, but it should be OK for someone who doesn't touch the partition table.
Also bear in mind that 'user level issues' may still exist if you install bad apps into your account, bad plists & weird cache issues will still occur.
You are also going to be juggling data based on what you guess are reasonable default sizes now - this could (and always does IMO) change in the future.
Think about how you can backup & restore this system too. I think having a few external disks in addition to bootable backups may be a more practical approach to moving data & restoring clean OS's.
It's up to you, personally I got tired of this approach years ago as some apps were insistent about saving data in their own locations - things like VirtualBox, Steam, Wine. It's tough to estimate how much these will bloat the user account or the boot partition. I do think it's reasonable to move the user home if you have a small SSD & a large spinning disk but that more out of necessity than choice.