To just say the obvious: What ever you do, you will technically ALWAYS need to reach LEO. Optimizing a launcher for direct ascent to ejection burn is possible, but usually making the launcher too specialized.
Yes.
By missions beyond LEO I don't mean direct ascent. I generally mean missions that are supposed to happen beyond LEO like a lunar landing missions. DIRECT might be cheap for missions to the ISS. But if NASA wants to go beyond LEO, to the Moon, they need to carry much more payload, no matter if it needs to be put into LEO first. They need a lunar lander, an earth departure stage, they need scientific equipment, they need to develope the whole stuff. There is a lot of people and work required. I doubt it would be possible to return to the Moon or to fly to Mars without a significant budget boost. I even think that NASA won't go to Mars on its own. They'll have to chose the international way just like they did for the ISS. I don't believe in a US flag on the surface of Mars. Less than ever do I expect a manned mission to Mars within my life time, well within the lifetime of most of the people who read this lines right now. It took less than a decade to virtually start at 0 and land on the Moon. And 4 decades later we come up with Ares I-X, which might never make it into LEO, and if at all, not within the next years anyway. Progress? You decide...
The whole thing that happens right now, looking for what can be done by current budget, is the wrong way in my point of view. On the other hand, NASA has no differenct choice yet. The only thing NASA really needs is more money. A lot of. Otherwise nothing will happen beyond LEO, just the way it didn't happen again since 1972. Skylab and the Shuttle already was the result of not enough money to continue missions beyond LEO. While the Shuttle was a real progress. Not in terms of going beyond LEO but in terms of engineering. But Skylab was a soapbox. Something that was build by remains of a past era, or at least an era that was going to become past due to low budget. A botch job, although that station was an amazing piece of hardware. To cut Apollo and decide for the Shuttle was a bad mistake though. It caused a huge gap, plus it did take away the capability of going beyond LEO for decades. Almost 30 years later we now have the outcome of that bad path. Again a huge gap and an uncertain future regarding missions beyond LEO. If NASA has to continue to struggle with low budget and is forced to continue with botch jobs, it'll be an endless loop of developing stuff of not being capable to go to the Moon, less than ever to Mars. The talk about extending the Shuttle flights and the ISS life time right into the 2020's already is a "good" indication...