There is no conflict between a fuel depot and a meticulously planned mission. It just becomes part of the mission. For example, using the fuel to fill up empty propellant tanks so when a spacecraft goes into a transfer orbit to the Moon, or GEO, it will be able to carry much more payload then if it had to depend on the fuel it carried into orbit from Earth.

Instead of building a bigger launcher, like a Saturn V, to seen astronauts to the Moon, you could use a smaller one, perhaps a Atlas V Heavy and multiple launches. One for the lunar lander, another for the crew vehicle, another for the booster to move the stack from Earth orbit to a lunar transfer orbit. Combine them at the ISS, fill-up the booster, and you are on the way to the Moon with the same payload that a single Saturn V launch would allow, but only using three existing Atlas V heavies instead having to build a new Saturn V class vehicle.