You CAN use USB risers in folding, but higher-end cards suffer a significant performance hit if you do so, ballpark 25-30% in some brief testing I've done on my Aorus GTX 1080 ti cards.
If you were seeing 500k on one, you either had a "pain" work unit type or there was something else limiting the card, even on a USB riser I normally see more like 800-900k on most work units (vs 1.2M AND UP on most work units on non-riser setups).
The hit is less on lower end cards, but still noticeable.

On the positive side, a riser-type rig is a LOT easier to keep cool, and USB risers are INFINITELY easier to work with than multiple "16x ribbon" type risers.

One REAL CPU core per GPU is definitely needed - "hyper-threaded" cores need not apply they can't keep up with higher-end cards and WILL throttle your performance badly.
More than one core per GPU does not help, as the folding client isn't coded to use more than one CPU core per "thread" and it runs one "thread" per GPU core.
If you DO have spare cores, you can use those for other stuff though - like folding on them or XMR mining.
Even REAL cores are starting to get marginal sometimes - I was doing some testing once on a G-series Pentium (G4560 or G4600 forget which offhand) and a single 1080 ti was loading one "real" core on that to over 90% average, and I THINK I was taking a small PPD hit on the GPU even so.

For 12 1080 ti cards in a rig, 12+ real core Threadripper or 12+ real core recent Intel server CPU are the only viable options for full PPD - but you're going to be impacted by USB risers as well even WITH enough CPU power.

Let us know when you manage to get listed on a MAJOR exchange - I've never even heard OF any of those exchanges before now.