The PIO are pretty great and not niche. Almost any embedded application needs mixed signal interfaces. You could say embedded applications are niche, but not that embedded applications needing mixed signal interfaces.
A serious warning: read the RP2350 errata carefully. You may be better off buying old 2040 inventory.
RP2350 adds secure boot and encrypted boot. I am working on a little hardware device for a CTF and selected it as my MCU so participants can't just dump the flash to grab the flags.
> read the RP2350 errata carefully
Even the latest rev? Can you elaborate a bit?
The smart engineer always reads the errata carefully.
Mixed signal means analog and digital
> Almost any embedded application needs mixed signal interfaces.
For the vast majority of embedded applications you can simply pick an MCU that has the hardware peripherals they need. That's why XMOS was never very successful. (They thought of this idea long ago.) Not saying it isn't cool.