Wait for NVIDIA 555 driver release, use a bleeding edge rolling release distro (like Arch or OpenSuse tumbleweed) to get explicit sync support and use Wayland instead of X11. Soon the pain will be over…
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Just use Mint.
I'm on Mint 20 and had an unreasonable number of monitor configurations. Initially tallscreen + square, then tallscreen + square + 32-inch HDTV, then tallscreen + widescreen + TV, then tallscreen + 42-inch HDTV (because I ran out of desk), then tallscreen + 42-inch HDTV + widescreen on the floor as a dedicated AGDQ window, and now I'm only using an enormous 4K TV.
I've had issues, but never "it can't handle it" issues. My little RX 580 occasionally produced a black frame on one monitor or other - I assume because none of them ever had identical refresh rates. The larger issue was instantly forgetting my monitor configuration every time one of them was unplugged or lost power. As if losing the square monitor caused the rotated screen to fall over.