Use of present technology suggests a 2 stage launcher to LEO. Stage 1 would initially be expendable and provide altitude and perhaps about half of orbital velocity. Stage 2 would enter LEO about empty and link up with an orbiting fuel dump. By refueling this would allow stage 2 and the payload to depart for moon orbit, a Lagrange point, or Mars. There stage 2 could again refuel at a fuel dump.
The ideal size would probably be smaller than the HLV designs suggested so far. The exact optimal size depends on how much the system is to be used. To make good use of ground facilities launchs should be fairly frequent.
A growth option would be to develop a reusable stage 1.