John:

The basic idea here is to get the most massive parts of a spacecraft
moving once, and then kept moving, while the 'disposable', lighter
parts of the missions - the crew, cargo and fuel - are added at the
source and removed at the destination.

I'm thinking BIG here. Big enough that the biological needs of the
crews are self-contained and self-sustaining. With enough shielding
to avoid having to worry about significant radiation exposure.
Whatever we want, because the whole thing is going to be accelerated
one time, and then kept moving with clever swings past source and
destination with fine-tuning of paths accomplished with efficient,
low-impulse engines.

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Moving out of gravity wells is the main fuel cost for both build and
supply.

The shear size in materials and cost to have such a vehicle manned
for Mars seems wasteful. A robotic craft should move consumables and
most equipment one-way only. Packing only additional sensors,
communications, navigation aids, and emergency supplies continuously.
The large manned systems supporting Mars exploration would be better
sited on Phobos/Deimos. The exploration crews should fast transit,
although a first slow manned transit could be made to set up such a
base and support crew.

The resources for the huge self-contained craft should be held back
until we commit to manned exploration outside Mars' orbit, but would
be essential in that role. Again I would keep this craft out and use
robotic craft to supply it, however it would loop back for refurbishing
at need.

One problem will be long-term crew selection. I don't think NASA will
commit to the profile necessary for distant station keeping. A loner,
craftsman, artisan, and engineer is very distant from a military, PhD,
social, and political personality. Doing long-term "PhDs in a can"
tests seem of limited value in developing the specification(IMO).
Crew profiles are better served interviewing desert prospectors and
the people who solo-crew Antarctic research stations during the
off-season. Any person who functions productively for years alone
and is still nice to visitors. These will be the people who must host
and at need rescue the exploration scientists.