Well, I'm not Beeple, but I'll try to answer the question anyway.
Honestly I've done it all — 4 monitors in a 2x2 grid, four side by side, two side by side, two side by side and one vertical. Honestly, what I took away from the experience is that monitor space is like the size of a bowl for goldfish. You'll pretty much always stretch out and figure out how to use screen real estate
When I simplified things down, I found I was happiest with one UWD, and a small second monitor off to the right. It's well suited for graphic design work, cus I can keep a document or Slack open on a small monitor and have a full UWD to handle all my toolbars and stuff.