One of the things I realized when reading Start Small, Stay Small was that a small enough niche is a barrier to entry:

If your company/product dominates a market that is pretty small, and, say, makes $100,000 a year from it, that's just not going to be an interesting target for bigger companies with the resources to outcompete you.

So the trick is to dominate the niche, and then automate, so that you're making that money without a great deal of day to day involvement.