Here is a first quick suggestion for a spacecraft configuration based on the early discussions, without any trace of vanity, I decided to name this configuration U0:
It is based on a small LANTR engine as main propulsion and main power source, the cargo and the crew being stacked above. I think a crew of two could be minimum there, while the primary structure could likely also be large enough to allow carrying 3-4 passengers. From an organisational POV, I think a crew of three might be smarter, having one person dedicated to the cargo handling and engineering duties, while the other two handle navigation and communication, and command and management.
The crew section and the engineering section can be separated in emergency, leaving the crew section as minimalist lifeboat. I think about putting a classic bipropellant outside the primary structure into four separate module (each with its own propellant resources and engines), for simpler servicing (I think disconnecting propellant lines in space is more work than it really saves weight). Those RCS modules could also be used for docking. Primary RCS would be using superheated hydrogen from the reactor core. There should be also enough electricity available to improve the ISP by using ArcJets - but I think its not necessary.
The communications gear is mostly placed into a gimballing communications mast, that can be placed between the cargo containers when no longer needed (eg, when docking), for making the spacecraft fit better into a limited approach cone.
There is a standard docking port on front (the drawing is not perfectly on scale - modelling is no self-purpose).
All stuff that could be a major explosion or radiation risk is put into the engineering section. The H2 tanks have a rather poor empty mass for a chemical rocket engine, but are more robust. All the H2 tanks are surrounded by a sunshade that reduces the need for refrigeration and recompression. This one also acts as first layer of MMOD protection and can easily be replaced even without docking the spacecraft to a space dock/station. Again, by using a LANTR, a lot of the structure can be build more massive and robust, than possible with chemical propulsion, allowing a longer lifetime of the spacecraft in space. I am still not fully sure where to put the small LOX tank for the LANTR, because the size of it is still unknown - it depends on how the propulsion should be optimized (or not, allowing more freedom for the crew). The separate cylindrical H2 tanks could also allow managing the CoG a bit, should the cargo be too uneven to use engine gimballing.
The LANTR reactor core is supposed to be one self-contained unit, that can be replaced and reprocessed by the manufacturer as whole, the nozzle extension can be replaced independently. All support equipment, that is not directly connected to the core is in front of the radiation shield structure. It is installed into modules that can again be replaced rather easily (at the expensive of more weight), that should be usually be hidden by panels with chevron louvers, allowing the heat of the turbines and pumps to be directly radiated into space,. Most of the flight time, the standard radiators should be enough for keeping the systems cooled, while using the main engine or afterwards for dumping decay heat, heavy duty radiators can be used. Maybe it makes sense to allow retracting them and protect them against MMODs, but right now I consider this unneeded complexity. Right now the standard radiators point backwards, away from the propellant tanks. Not sure if this is really the best choice, maybe its better to extend the radiation shield structure a bit more and place them at the sides, allowing to use the radiation shield also as additional sunshield during cruise phases.
The design right now looks rather slick and cylindrical, but I am sure this will change later. Aerodynamics are not needed. The crew module looks conical towards the docking port now, but even that is not necessary. It could be come more complex shaped. Especially I think about putting many consumables and parts with a short lifetime into modules on the outside of the hull, for easier servicing and isolating possible damage better (should one such module get badly damaged by a MMOD strike, the rest of the spacecraft should only get slightly damaged)
Again, its just a first quick drawing done during the idle holiday hours. I hope I will see some less boring ideas from others here.