I was so excited for the ATSAMD21 series when I first came across it maybe five or six years ago, because on paper it had most of everything I was looking for while remaining approachable for single-man dev teams and home(lab) assembly. Like OP, I found it extremely difficult to successfully use in practice, and have since then migrated to STMicroelectronics' offerings (STM32 MCUs, available in a huge range that includes Cortex-M0, M3, M4, M7, and now M33 for ARMv8-M). They're much more intimidating on paper, but they actually work like it says on the sticker.
I have a fondness for MIPS as I first learned CPU architecture and more advanced compiler design against it, but I'm surprised OP didn't go with ARMv7 support. The bi-endianness is almost a non-issue as it's effectively a Little Endian architecture with a Big Endian toggle for backwards compatibility - I can't say I'm positive, but my gut instinct would be that it's been forever since ARMv3 shipped defaulting to Little Endian, and most (if not all) of the kernel code has been migrated to Little Endian since then to unify with the most popular targets.
I have a fondness for MIPS as I first learned CPU architecture and more advanced compiler design against it, but I'm surprised OP didn't go with ARMv7 support. The bi-endianness is almost a non-issue as it's effectively a Little Endian architecture with a Big Endian toggle for backwards compatibility - I can't say I'm positive, but my gut instinct would be that it's been forever since ARMv3 shipped defaulting to Little Endian, and most (if not all) of the kernel code has been migrated to Little Endian since then to unify with the most popular targets.