The layering
Settings writes to the same keys you can poke in regedit, then performs validation, policy-aware no-ops, and Explorer reload choreography. Regedit accepts the exact byte you typed, and makes the consequences your own. Same hive; different error model.
Decision table for mortals
The privileged app-operational angle: a good tool can still write HKCU directly, provided it documents every value — the restore semantics don't get worse because the write had a UI; they get worse when provenance was never recorded. Values with behavior contracts deserve a mechanic who writes them down.