In PGB mode 2 the CPU is still able to run (within a limited address range) and can use register FF75 "PGBIO" for limited input and output on some cartridge pins (and/or the link port for IO).
I don't think it's widely known (only found and documented somewhat recently) that there is a way for cartridges to directly drive the Game Boy Color LCD, bypassing the CPU/PPU (PGB Modes). At that point though it becomes even less of a Game Boy game than what the Wolfenstein and other carts are doing.
Also related: "There oughta be GTA5 for the Game Boy" about a Wifi cartridge that can stream video (gameplay, etc) directly to the GB screen.
https://there.oughta.be/gta5-for-the-game-boy
For GBDK-2020 we've been using the 6502 support in SDCC to support the NES as a target console for about 2 years alongside the existing Game Boy and SMS/Game Gear targets.
The 6502 port has been usable, but doesn't seem fully mature. There has been a lot of code churn for it during the last 12 months compared to the z80/sm83 ports as it gets improved. Recently (their recommended pre-release build 15614) this seems to have resulted in some breaking regressions that we haven't fully tracked down.
Perhaps this port is getting less testing coverage than the z80/sm83 port. Unsure. The majority of the 6502 work seems to be done by a newer member of their team, with the longer term members seeming to be somewhat hands-off. That might be an additional factor.
Edit: BTW, the 6502 port in SDCC at build 15267 (~4.5.0+) has been reasonably stable and usable, and is what we based our last GBDK-2020 release on (6 months ago).
With regard to code size in this comparison someone associated with llvm-mos remarked that some factors are: their libc is written in C and tries to be multi-platform friendly, stdio takes up space, the division functions are large, and their float support is not asm optimized.
Great project btw