In the long term, the most obvious major money-making opportunities are asteroid mining and space power generation. Both of these require an enormous up-front investment, but have a lot of potential. I did a quick study on this back in 1989, using best figures on asteroid composition and numbers taken from an almanac on resources, and found that a single half-mile nickel-iron asteroid would contain amounts of some metallic elements (nickel, cobalt, platinum) that would dwarf the known economically-recoverable world reserves. If I could figure out how to post Word tables on this thing, I'd post the paper here.

Space power generation, or building large satellites in space to beam power to Earth, also takes a huge investment. However, it is instructive to note the amount of money--never mind lives--we spend working with and protecting Mideastern oil interests. The cost-benefit analysis of solar power satellites may not be as bad as most people think.

In the short run, I think space tourism is the way to go. A viable and profitable space tourist industry can be started with suborbital vehicles, which are much easier to develop than orbital ones, yet can be used as stepping stones to an orbital business and beyond. A number of organizations are already working this route. For more money, but a lot less technological development, Russian Soyuz and space station technologies could be used to build a small, but practical orbital tourist destination. Mircorp is looking at this. All it would take is enough cash.