You can reliably run DOS, Win, Linux applications of almost any vintage with the right translation layer / emulator, but there's a black hole of MacOS apps circa 2002-2012 that just no longer runs on anything, even later Intel Macs.
I used to enjoy a cute little Pacman clone called Pac the Man X, for example, and I just don't know how I could run this today. Seems to reliably take down any emulator I've thrown at it - presumably it's using some kind of graphics acceleration that's not emulated. (Suggestions welcome.)