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macOS treats ports equally on separate cards, assuming both have Mac drivers. It will work the same as if all ports were on a single card. Arrange your displays as normal, move cursor and windows around as normal.
Do you have an opinion on the WX4100? The most advanced stuff I’d be doing video wise is Illustrator, Photoshop, Premiere, and Logic/Cubase, I don’t see where any of those would need anything insanely powerful. Between the 4100, 5100 and 7100, if running 2, which do you think would be the most reliable and stable while giving adequate performance?

I’m not sure what it was that made the FirePro act up, I don’t see how j could’ve messed up my Pixlas mod, it seems to me like there was a power issue or flash/software issue or something - every time there was a strain on the machine it would implode on itself.
 
The WX-4100 is limited to 4GB of VRAM. Compare the WX-x100 cards. With gamers today going to 16GB, I was leery of going so low. Recall that macOS uses a layered GUI, and you plan to run 3-4 4K monitors off each card. Possibly even in HDR. Note these cards were released around 2016, they're not insanely powerful by any metric today.

I have a WX-7100. I went up the scale, on the theory that a more powerful card has more cooling capacity. For a given load, the more powerful card would run quieter, because it's loafing. A 4100 might be maxed out with your expected load.

Suggest using a volt meter to pin out your connectors coming off the PIXLAS mod. Make sure they're all +12 or Ground in the right locations. A missing ground connection could turn an 8-pin connector effectively into a 6-pin connector. Otherwise, I suspect your new old FirePro is just failing. Caps drying out, or the fan losing power.
 
You are just running a single WX7100, correct? I suppose it’s a bit like the old adage about choosing the V8 over the V6 in a big vehicle pertaining to gas mileage… the V6 has to work much harder to just move it, but the V8 moves with ease and doesn’t require as much input (throttle), yeah?

However in the context of running 2 of those things, would I be in a similar or the same situation power/draw-wise…?

Also, I read something about 4,1s being able to accommodate 8 screens, and 5,1s being limited to 6… not that I would plan on running 2 more, but being that my machine is a 4,1 to 5,1 convert, which rule would apply to my machine? If running 2x WX7100s can allow 8, it’s always nice to know I “could”, if I wanted to.
 
The Wikipedia link I gave includes the output ports on each Pro card, in the right-most column. There's even the WX-9100 at the bottom, with 6x mini-DP. Though it's 2-slots wide, and based on the Vega architecture, while the lesser cards are equivalent to RX4xx and RX5xx cards.

I bought a single WX-7100 while trying to fit two GPUs in my system, along with other cards. It was adequate in terms of graphics power - I didn't notice any lag vs my usual RX-580. But my Mac Pro is in my bedroom, and I didn't like the slightly greater fan noise from using a single-slot card. It's also possible my (used) WX-7100 just needs fresh heatsink grease to return to silent operation.

Anyway, I went back to my RX-580. My WX-7100 is not currently being used - it's in the spare pool.
 
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