Re: Oh crap.
Going back to the Moon doesn't solve any more problems than being on the ISS. The shuttle actually might have taught us some new things about Earth-to-orbit flight, which is still the biggest problem of space travel, from which most of the other problems flow. But I think the lesson we seem to have learned, was that it's not worth doing again. I'm not sure that's the correct lesson, but then I still don't think we have the technical solutiosn (either engines or material science) to build a practical Earth-to-orbit taxi.
You can't just dismiss the radiation problems with water. To get enough water to surround your astronauts, you're going to need a bloody big ship. Plus an engine that can push it, plus the actual water itself. That ship will need to be assembled in orbit. One of the things the ISS was designed to teach us. Current rockets would give us a pretty slow trip to Mars, or a huge ship, with big fuel tanks. Though modern engine research and testing (some of it being done, or about to be, on the ISS.
One of the problems we have is that there are only 3 currently practical things to do in space. Go to the Moon, do the ISS thing, or repair satellites. There's notthing else close enough to the Earth to do safely. Repairing satellites is incredibly hard and expensive. You've complained about the cost of the ISS, but that's only keeping 6 people in orbit. To repair satellites would need more, with more resources in orbit - and so at current costs would probably be uneconomic. Which means we need to cut the costs of living in space, and of Earth-to-orbit flight, which means we need the experience of the ISS and the shuttle. Here the ISS also helps, because of COTS. Space X may be about to cut costs by a huge amount, which might make more things possible.
I really don't see any possibility of deeper manned space exploration without the ISS, or something like it. This is the kind of expensive, only semi-useful, thing that government does best. We're learning loads of stuff, but the scienctific gains are probably far too expensive compared to what could be funded on Earth. However, we need this in-space experience before the commercial sector can go do it's thing. We need a platform to test growing plants, because that's going to have to happen in long-term space travel, or people are going to need awfully big ships. That still needs to be studied.
For example 1 person needs say 5kg of supplies per day - food/water/oxygen/whatever. It's 2 years to Mars. That's over 3.5 tonnes of supplies, per astronaut. Maybe that's a bit too much, but a Dragon can get 2.5 tonnes to orbit. So if you want to take 6 astronauts to Mars, that's 8 Dragon flights, to put them, and their dinner up. Now you've got to get the ship up there. Including a couple of Mars landers. If they're to spend more than a token couple of days on Mars, then you need to give them spare landers, and plenty of fuel. Because to stay on Mars for more than a few days, they'll need tons of cargo, radiation shielding (or digging equipment). All this makes the ship bigger, and more expensive. We're talking low tens of billions, a pointless fly-by or a suicide mission.
Make that an asteroid, and things get easier. You've still got the living in space thing, so the huge ship with radiation shielding and loads-a-food. But the journey can be shorter (hence a smaller ship), if you pick the right asteroid. You can do without landers, and do your exploration with suits and backpack jets. Then maybe do some mining/prospecting. Maybe attach a dirty great rocket, and push the thing to Earth orbit, to build spacestation on? But even that's at the edge of our technical capabilities, and beyond our current political/budget capabilities.
If you want to argue this means giving up on manned spaceflight, and going all robot probe-y - then you're possibly correct. But I'm unsure if I'm on board with that. I'm certainly not as inspired by it. I want to see people in space, I want to harness all those lovely free resources up there, if it's possible. The ISS helps to tell us if it is possible. The robots can maybe tell us if the asteroids are full of free resources. But manned flight any further than the geo-magnetic field will probably be horrifically expensive for decades even in the best case scenario. So the only pracitcal chance of a trip to Mars is probably a space race with China, and that would probably only happen if we got into some kind of Cold War II. Not a price I'd want to pay for the exploration I'd like to see. So to me, the answer is making permanent orbital presence possible (and cheaper), the economics being covered by whatever goodies can be manufactured best in micro-gravity, and satellite repair. Then try to capture an asteroid and mine it. If we could get one with hydrocarbons, then we wouldn't have to keep boosting rocket fuel into orbit. Ditto for growing plants for food/oxygen. Then we could try orbital manufacturing. It's a chicken and egg problem, unless we can solve the horrific costs of Earth-to-orbit. How do you make a space based economy viable, when it costs so damned much to start up?