It might be a good idea to start with a small (unmanned) fully reusable system and slowly scale it up over decades.
I am also partial to ramjet (if feasible) for the first stage, at least up to whatever speed makes sense. All-rocket designs may be simpler, cheaper, and more reliable than ramjet. It remains to be seen.
Anyway, starting small and expanding each generation by a factor of four might very well be the best way.
"Complex systems that work evolve from simple systems that work, not from complex systems that do not work."
