As someone has stated on the forums you have to optimize both for in-game cost (funds) and player cost. Any design that requires hours of repetitive gameplay to achieve something is not fun to play. My cents to the problem: Tanking in LKO is a must. It allows simpler interplanetary designs. Bigger interplanetary vehicles may be launched into orbit with empty fuel tanks or the last ascending stage (that inserts the vahicle into stable orbit) can be reused for interplanetary burn after refuel. Tanking interplanetary ships by Mun or Minmus is not good for interplanetary missions because Oberth effect dows not work out well there. Even launch window timing is worse on a bigger orbit. Mun or Minmus mining would be the most efficient but takes too much player time. Because the fuel must be ascended brought back to LKO and tanker must return and land on Mun each time. I would only mine satellites of remote planets for fuel (Bop mining rig is already set up). SSTO spaceship is also efficient but too tedious to bring meaningful amount to LKO. For me the best option is rocketing fuel to LKO, fueling the target vehicle directly and return the tanker to Kerbin surface for refunds. I use a 7 Mammoth driven 7*3 (or 7*4 dont remember exactly) S3-14400 tanks as the tanker. The ascent is helped by some SRB-s that are jettysoned and the stabilizer wings break on Kerbin reentry but otherwise the craft is reusable. The 7 Mammoth engines and the huge Kerbodyne fuel tanks return to Kerbin surface braking with parachutes and the main engines and can be recovered for funds. A single set of the S3-14400 can be used to fuel the target the others are emptied during the ascent and return. That is 288 or 216 net tonnes of LFO. A single launch costs about 1M funds and about 420000 is returned after recovery. But I havent checked the numbers I just write them from my memory. A single launch refuels multiple interplanetary missions for me (I aim low weight for my designs).