The challenge as I see it is that we're not a 'space program'. We're sort of running one and managing other stuff on the side and being a pilot, scientist and engineer. The human race has, what, one permanently crewed space vessel in orbit of this planet? If we were (as I'm sure many KSP players have or had) maintaining a Kerballed platform around Kerbin, one around Mun, another around Minmus, then going to Duna becomes really tedious if you have to constantly take your Duna flight out of time warp to launch and dock a resupply mission to an occupied station. In a hypothetical 'real world', you'd delegate that to your likely eventual replacement, or subcontract it to a private space company (multiplayer options, but who'd want to be driving the food truck on a schedule?). As Boss of the space program, you simply could not manage all that. You're going to focus on the thing that carries the greatest risk to your prized little green assets or open up the next big opportunity.
So while the concept of LS is attractive to me (and there are elegant models and outcomes proposed here), the logistics of maintaining a presence in space are painful without some level of automation running in the background.