If the Seeed XIAO SAMD21 is working well enough for you, then you can certainly stick with it.
RP2040 with QMK would offer easier reprogramming of the keys / buttons and also lets you do more with the keys. With Vial or Via, which is built on top of QMK, you can easily change things in a nice GUI. You can double tap a key, triple tap, tap & hold, double tap & hold, press two buttons together, all with different functions. You can send macros, scroll movement, mouse buttons. All through an easy point-and-click GUI. Vial has Win/Linux/Mac desktop apps and a web browser GUI as well.
Downside is that it will take more work to set up initially. Especially since you have something already working.
With a RP2040, programming (putting Vial/Via & QMK code on it) doesn’t even require setting up an Arduino IDE.
I put Vial QMK on my 15-button mouse using a small RP2040 board.
As long as there is room, making a USB-C male-to-male adapter would be fine. Connecting them with short flexible wires, then you can position it however you need. I’ve made custom USB-C cables. Space is the question, though. What’s the internal space inside your enclosure?