I would choose a port of DragonFlyBSD with ZFS on AMD x64 hardware + FS-UAE for backwards compatibility.
I would customize its GUI interface to be more Amiga-like and would not support all hardware devices around, but just the three or four more widely available from different vendors (so no wasted resources in trying to support every piece of hardware out there).
BTW, DragonFlyBSD has some distant Amiga heritage (Matt Dillon of Dice C fame is its author). And many concepts of its design are taken from AmigaOS.
