What I think will work - not claiming that it will actually work - based on history:
Invest in companies that are generating a lot of cash and a lot of profits, have a moat/USP/technology advantage, and are at the forefront of where the world is headed in terms of trends, or at least are following a sustainable trend. Yes, you need to identify the company. Yes, you need to take decisions: INTC vs AMD (1980s), YHOO vs GOOGL (2000s). But it gives you a much better chance of seeing a profit in your lifetime than index investing. You can still index invest, but only an amount you can "set and forget". This gives you the best of both worlds.
Edit: (1) What I posted above is for long periods of no movement of stocks except downwards, as I believe we are going to see. (2) Index investing will work eventually and that is what I said above as well. The point is, the time period required for that. (3) I thought of posting this on my blog tomorrow, but it is past midnight here, and I wanted to see what HNers think. It is interesting to see the different opinions. Time may change some of your opinions (not about "index investing will not work" - that is not what I said above - but rather, about the protection offered by diversification, and what diversification actually means. Also, quoting this part again: "the average person does not have the stomach to see their investment going down for years, unless that investment is small enough to tolerate (in which case it is not enough to make a big difference, for most people)").