Even if you stripped off the wings, landing gear, etc. from an orbiter, you'd still have too much dead weight. The structure of the orbiter was designed to handle the launch, reentry, and landing loads. It would be massively overbuilt for lunar shuttle (LEO to lunar orbit and back) purposes. In that sense, it'd be a lot more effective to build a new vehicle designed for the expected loads rather than trying to make the Shuttle do something it clearly wasn't designed to do.

By way of analogy, if we tried really hard, we could convert a nuclear powered aircraft carrier into a submarine. It'd require sealing a lot of the decks and flooding the lower decks as ballast tanks but, at least in theory, it could be done. However, in the end, you'd end up with a pretty lousy submarine that wouldn't be very fast (too much drag) and couldn't dive very deep because it wasn't designed for that type of load.

I would like to use as much off-the-shelf technology as possible for things like life support, heat control, auxillary propulstion (attitude contol), avionics, etc. Still, the new vehicle should start with a relatively clean sheet of paper to do it right.

You'll need a crew module capable of carrying a reasonable number of people, say 5-10. That will require electricity (fuel cells or solar arrays that could be retracted for aerobraking), consumables, life support, avionics, attitude control, thermal control, etc.

You'll need the aerobraking and propulsion system sufficient for the tasks.

How often would we be returning payloads from the moon? I really don't think that would happen very often. Furthermore, if you use something like the Russian's new inflatable heat shield, you might not need to enclose the cargo bay at all. If that's the case, then we could really reduce the structural mass.

Look at my post about the design approach I use and you'll see why eliminating dead weight is so important if you're going to build a viable system. Work backwards step by step and see how the beginning of flight mass snowballs for every additional kilogram of mass at the end of the flight. Each additional kilogram of mass at the end of flight can easily end up requiring several additional kilograms of propellant at the beginning of the flight. Remember, it takes propellant to accelerate propellant and more propellant means bigger (heavier) fuel tanks, etc. And each additional kilogram of propellant required at the beginning of flight means a lot of increased expense, especially if we have to launch the propellant from Earth.