I've been working with getting games from 1995+ working on modern systems over the past two years, and honestly the biggest incompatibilities I've seen have been in the registry. Combined with some redirected filesystem calls, I really think you could get 98% of games working in a portable fashion.

The problem I have with some of these GoG releases is they just patch out buttons for things like networking, when features like local IPX multiplayer can still work with shims.