Speaking about the snes, i don't think that one core should be abandonned since all the porting has been made for both 1.39 and 1.43 and even if 1.39 usually performs better, it's not always the case (try to play pilotwings with fast core for example.).
But i guess lion want to know if he should go with picodrive, genesis plus gx or gens as a base for megadrive.
If we think about the pc engine, you could use hugo, mednafen, ootake...
A good start could be to see what have been already done on the dingoo (or dingux) and on similar handhelds (gp2x, wiz, caanoo)... or home console like the dreamcast or xbox1.
The major limitation could be the lack of a proper port of a 68000 core in mips asm (when those exist for arm cpu). I don't think megadrive needs this but if you want proper mega cd with mp3 support, it could be really usefull.