For me, obviously it’s great to work with the top affiliates. It’s probably more rewarding on a personal level to work with smaller affiliates, lending my expertise to help them grow in to top affiliates!
On another note, I currently represent a relatively small affiliate program, looking to grow, and we are certainly on the hunt for those smaller affiliates in order to compete. So with that in mind, I think the age, budget and size of the program also effects target affiliates.