So, is it possible to launch games with an external command instead of a libretro core? This would be great in case of C64, Amiga and Wii for example. RetroArch is a great frontend, would be nice to have this feature in cases where there isn’t a proper libretro core.
No, you would have to use something higher level, like hyperspin.
Figured as much. I’m currently using Emulationstation (the only decent alternative for Linux), but it would be great to be able to use RetroArch as the primary frontend. I realize it might not be according to your goals, but please consider 
Perhaps RetroArch could look for a command in .info files that do not have a matching core.so, or something along those lines.