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.
I very recently upgraded from a dual fullhd to a dual 4k setup and I was genuinely surprised how little problems I had setting everything up to the high DPI displays. I am genuinely interested in hearing what pitfalls might still await me.
It doesn't affect all monitors, but some DPIs really don't play well with X. The fractional scaling you get on Wayland leads to some element of blur instead, but that's a far lesser evil, the jank is a bigger issue IMO.
Once you've set it up it works pretty well though.
Now if only I could remember what I did to get it working nicely...(luckily I've had the same installation of XFCE on my machine for the past 5 years so haven't had to fiddle with that in a while)
But now I have so much screen real estate, I'm almost considering using a tiling window manager.