We might not need a big HLV for a while, depending on how well propellant depots work. And we might be able to get by with something much smaller than Saturn V for a long time.
A heavy lift vehicle can simplify operations, and can be the most cost effective launcher at sufficient flight rates, but most of the kind of missions that need a HLV also need very expensive spacecraft, so it will be very difficult for NASA to fund the high flight rate that makes heavy lift cost effective.
We have a proposal from JSC for a 110 tonne to LEO Shuttle derived launch vehicle, with estimated operating costs that approximate fixed costs of $2 billion a year and $300 million a launch on top of that. Assuming a propellant depot to avoid manifest inefficiency, three would be needed for a pair of Orion + Altair sortie missions, or $2.9 billion a year, not counting the spacecraft.
With a practical propellant depot in orbit the same payload mass could be launched by a dozen uprated Delta IVH launchers with RS-68A engines. If we assume those launches are allocated 90% of fixed costs of $500 million and marginal costs of $170 million per launch (probably high at that flight rate) you spend about $2.5 billion.
The biggest problem with the SDLV is that you're stuck with the fixed costs even when you don't have that many, or even any, suitable payloads.
And even if you can justify the high flight rate that makes a heavy lift vehicle cost-effective, it takes a long time to recoup the development cost of a big launcher. JSC estimates $8 billion for their plan, which keeps the design as similar as possible to the Shuttle. This design keeps development costs down by keeping changes to Shuttle components and infrastructure to a minimum, but would be handicapped by the higher marginal cost of the side-mount carrier and a more restricted shroud than in-line designs.
That said, orbital transfer and storage of cryogenic propellant may be more difficult than proponents think. That might make an HLV the optimal solution.
However, Ed Kyle has an interesting post on another way to do a sustainable manned program here:
Using a storable earth departure stage requires more mass in LEO per mission than LH, but you can use existing EELVs and avoid the huge fixed cost of a dedicated NASA-owned HLV.
With low boiloff LH storage you can avoid the performance hit of storable propellant, and that technology is baselined for Mars in NASA's latest study. Low boiloff methane propulsion is also baselined for Mars. But even if these technologies prove difficult, a storable stage can work as a fallback.
Although Ed Kyle would probably prefer to go to the moon first, a big storable stage is also an enabler for asteroid missions.
In short, we may be able to do a very respectable human space flight program beyond LEO without a huge HLV. With propellant transfer in orbit, the ability to put 35-40 tonnes in LEO would enable a robust program earth to either Near Earth Objects or the Moon. Deferring a decision to build a big HLV until we know more, as Obama’s NASA proposes, makes a lot of economic sense.
The biggest obstacle to this sensible idea is political: a number of people in Congress like the money the current plan sends to their districts very much.
In fairness, there’s a principled argument for a Shuttle derived launch vehicle as well: Shuttle solid boosters and main engines are powerful and reliable, and if we disperse the teams that build and launch them we will lose a capability we may never get back.