More/more flexible PIO instructions: branching is very limited, you can only arbitrarily SET up to 5 pins or pindirs at once (increasing to 8 would be a godsend), stalling with a sideset repeatedly executes the sideset, etc... I could go on.
Memory mapped PSRAM: I made a library to assist with accessing SPI PSRAM but it's still just functions to get/set groups of bytes. An intelligent cache around it would also mitigate the much higher latency of accessing PSRAM as well.
More SRAM: everyone can always use more RAM!
More GPIOs: everyone can always use more GPIOs!
My pet projects with the Pico and clones involve interfacing with an 8-bit processor, and the RP2040 just doesn’t expose enough pins for the full data, address, and control busses AND actually doing something interesting with the outside world.
Another dedicated USB PHY peripheral would also be great, a lot of people lose a PIO block to adding a second USB port. Obviously this also shows the power of PIO, but it’s nice to be able to reserve those blocks for more obscure physical things.
I bet a lot of people would like more analog pins, the Teensy provides a lot more, for example.
Or more pins and more PIO as well.
I guess more SRAM wouldn't hurt either.