> dual monitor setups that aren't the same.

Absolutely categorically false: I daily-drove such a config on openSUSE for 4 years, 9-5 Mon-Fri.

One portrait, one landscape: fine. 2 portrait flanking one landscape: fine. Laptop + 2 external displays, 1 big in portrait, 1 small in landscape: fine. 2 screens, vertically stacked: fine. 2 side-by-side, one big one small: fine.

Everything works exactly as expected. Panels stay put. Some apps can't remember their positions but they can't on any WM or desktop.

Very dissimilar resolutions gets tricky but that's down to Xinerama not Xfce. It's true on all X11 desktops.

Xfce can do fractional scaling on a per-display basis to get on-screen features the same size, but it results in some displays getting slightly blurry. Tolerable for short-term use but not all day every day, for me.

But Xfce is 100% usable in heterogenous multihead and indeed handles this as well or better than almost any other mainstream X11-based desktop.