The key to any setting - no matter what genre you are working in - is plausibility. The universe has to at least have internal logic to it, even if that logic might not work in the real world. It has to feel real, as if it is something that could exist, or the suspension of disbelief required for a novel to work is almost impossible to take. With this setting, I face this problem in spades, but fortunately a lot of extremely smart people have been working on this for a long time. The key question is this: Why Conquer Space? Evidently science and the betterment of mankind isn’t a sufficient goal, or there would be men walking on Titan today. (Yes, we could have done it if we’d wanted to. The money is certainly there.) So - what’s out there, waiting for us, in the near-future - with no major scientific breakthroughs required.
The key here is realism. It would be all too easy for me to invent something to make it work, say the discovery of alien artefacts - something on the Moon that has samples of soil from Mars, Mercury, Titan, Pluto - giving us a reason to go looking and see what might be out there. That could be an interesting story, but I want to do ‘How the Solar System Was Won’, try and write stories set in the future that I think can happen, that I hope - with increasing optimism, oddly enough - will happen. No space elevators, no magic wiffle drive, nothing that isn’t on the drawing boards right now.
First of all, tourism. By the end of this decade, there will be at least three, possibly as many as five different ways of getting into space - Soyuz, Shenzhou, Dragon, almost certainly CST-100, a chance of an Indian capsule design. At least two of these - Soyuz and Dragon - will be available for private individuals, and that means space hotels at last. Yes, the cost is going to be high, but there are people willing to pay it, and the cost will come down rapidly. While there will be a lot of adventurers wanting the experience, far more, I suspect, will be researchers running experiment packages. Taking the price into the low tens of millions puts it in range of a lot of companies and small countries - and don’t rule out the prestige factor of having an astronaut. I can easily see countries such as Argentina, Malaysia, hell North Korea paying for one of their citizens to spend a few weeks in space.
That’s only going to get easier, not harder, and the cost will go down - because it now seems increasingly certain that there will be functioning spaceplanes again in a decade or so. The plethora of capsules are going to tide us over, and yes, I’m talking about Skylon. Whether Reaction Engines themselves pulls it off or not, the technology seems to be working, and that means someone will do it. Probably more than one - in twenty years you could easily see Airbus going up against Boeing in this new frontier, likely a Chinese variant as well. (Maybe even a Russian one. They built Buran, and all that research and development could eventually see some practical use.) The Skylon baseline can put thirty people into LEO...and that’s enough to kickstart space tourism. When it costs six figures, then it dips down into a much larger pool of people willing to pay for it, and you start getting some serious work here.
Then comes commerce. First of all, solar power satellites might at last get some traction. While I believe that fusion is coming up by the middle of the century - slowly and steadily, we’re getting there at long last - it’s still going to be expensive, and I can see someone getting rich building orbital power stations to supply Third World countries. Yes, you can build them on the ground. Theoretically. But in the middle of a war zone, or an area suffering disasters? What’s easier, building a huge solar away in an unpopulated desert crawling with militia or a microwave receiving station in a city under government control? Build one array in orbit, and you can use it anywhere you like on Earth.
Of greater import will be the refining of asteroids. Periodically, there are plenty that get close enough to Earth in terms of delta-v that getting there won’t be a problem. I’m uncertain that they could operate entirely remotely; I believe that man-tended mines will be the likely outcome. Head out to an asteroid, do a proper survey and set up the equipment, then come back in four or five years to collect your platinum, gold, silver. Keeping weight down will be key, so the actual processing will likely take place on the asteroid itself; easier to build a processing plant and ship it to the asteroid than hurl tens of thousands of tons of dead ore around, and I don’t think moving asteroids nearer Earth is going to be a popular thing to do.
That will mean the construction of an orbital - and possibly, beyond orbital - infrastructure. Water’s going to be key, and that’s abundant enough in space. Sorry to disappoint the Lunar Colonists, but it’ll come from asteroids - or from the Martian moons. Hurled from deep space into Earth orbit to use as fuel. (And yes, that implies that before too long, there will be mining of near-Mars asteroids as well as near-Earth asteroids. Once you’ve built the fuel extraction plant on Phobos, you’re on the way.)
As for science, well, LEO gets you halfway to anywhere. I don’t really think that we’re going to properly colonize space in the 21st Century - though within the 2020s, there will be people living in LEO permanently. I can see billionaires buying modules of the space hotel and retiring up there to extend their lifespan. We’re talking fingers of one hand, though, at least for the first half of the century. That means no colonies on the Moon or Mars, but there will certainly be scientific bases, probably more than one, at least on the Moon. I can see the United States and China certainly operating their own outposts, heading up international consortia; Europe, Russia and Japan are also possibilities. Mars could be even more so, oddly enough. I don’t think Mars One will explore anything other than strange new worlds of litigation, but there will be private Mars efforts. Which will fail. I can’t see a Jamestown, but I can certainly see a Roanoke. My guess is an International Venus Station in orbit, and likely expeditions to Mercury, a few of the asteroids, and Callisto in the first half of the century.
It’s all about access, you see. We’re on the verge of it opening up, and there are companies right now working on this; Planetary Resources has the funding potential to do the job if they stick at it, and someone’s going to want to make billions exploiting asteroids. A new gold rush, and one that is a lot easier to operate from LEO. None of this requires any really new technology to pull off; VASMIR ships operated with Lockheed-Martin fusion reactors, anyone? Nuclear-Thermal Rockets, which we really could have had for decades already if we’d paid for them? I don’t need to make anything up to create an interesting setting in space. It’s all there already, waiting.