I am using Reaper with the guitar plugged directly into my interface (Scarlet 2-i2), and I get a decent sound with the TSE 808 -> TSE x50 -> Poulin LeCab -> ReEq. However, I have a high noise threhold when cranking the gain for the sound that i want, to the point where it interferes with my regular signal (even with a noise gate). Would it potentially reduce the noise floor if I were to use one or more USB opto-isolators, or would I be better off getting a device with paired transformers to break the electrical chain and reduce noise/ground loops?
If the noise is induced in the pickups - eg from your monitor screen or fluorescent lighting, then no amount of electrical isolation will cure it.
The only cure is switching off the offending sources, or moving away from them.
A long-shot 3rd option is to get an old Line6 Variax, which doesn't use magnetic pickups at all & is therefore induced-voltage-free.