Ubuntu is probably the way to go on the Pi if you're looking for compatibility. The 32 bit version is ARMv7 instead of ARMv6 with HF packages as Raspbian is. The 64 bit version is ARMv8. It's an official version from Canonical so you don't have to worry about some person abandoning their build or compiling your own packages all the time. With the newer CPU in the Pi 4 it's possible for them to support >4G models in the future but they aren't really interested in targeting $100+ use cases so it'll never make a "great" desktop. Useful as a fanless device that can run standard code though.

If you hack into PCIe you'd lose the USB. It's only a single x1 connection. I suppose you could hack a PCIe switch on top of that but even so it's x1 so it was already oversubscribed just hosting the USB 3 interfaces.