Running 3 monitors here. Mixed DPI (laptop is 4K, both external displays are 1080P). Ubuntu with Gnome running on Wayland. A few of the applications I use still don't support Wayland scaling properly (meaning they need to stay on whichever monitor they were launched, lest their zoom level get messed up) but it's getting better and all of the built-in Gnome stuff works great.
This genuinely took zero configuration on my part, besides perhaps going into the Display control panel and changing the zoom level for the 4K display.
Depends on your setup. I run a fairly custom setup without a DE and such and I just use xrandr(arandr) and saved the layouts. I haven't bothered to make anything happen automatically since I have a few different monitor setups, so I just run the scripts manually.
