IMHO the key for Humanity's exapnsion into space lies in the industrialization of space. As long as we keep using earthbound infrastructure for the manufacture and construction of all materials used in spaceflight, we are going to be stuck down here with extreme launch costs for anything and with an inability to construct anything big in space without it being very modular.
What we need is infrastructure in space - that is, on the moon and in LaGrange points, using materials mined from the moon and from near-earth asteroids to construct factories in orbit. Remember - the highest cost of spaceflight is the cost to launch from earth. With enough infrastructure, we will only have to send the Humans up with enough life-support and fuel to reach the orbital facilities; and even this cost could be minimized by aerodynamically-assited launch-craft (X-33 IIRC, but the program was cancelled by the government during budget cuts

).
The initial investment would be staggering, but otherwise we're going to continue to pay massive launch costs for every unmanned sattelite of manned spacecraft.
The Apollo Project was basically a single-goal mission, aiming at landing an American on the moon for PR and propaganda purposes, with military applications, technological development and pure science coming a distant second. No infrastructure was built off earth, and once the goal was reached the entire prospect for further Apollo-style moonflights got less and less appealing from nearly any POV, especially due to the facts that robots could easily return moonrocks back to earth at far lower costs as Humans. To return to the moon a more systematic approach is needed.
See
this site for ideas about what I'm talking about.
The overall problem is IMHO political in nature rather than technical - we COULD colonize space; those in power simply choose not to as their current interests lie in other places. So either we remove the ones in power and take control of our destinies, or we could wait for their interests to shift and hope that they'll change their minds early enough to get us out of here before all of our non-renewable resources burn out and our ecosystem dies.