The most profitable routes from my experience are the 10~25 million range airports to 5~15 million range. Being in the top airports mean lot of competition. Prices drop like crazy. You just can't have 6 mega-airports as bases.
It also depends on the planes and the location of the airports. After extensive research the round before, last round, I achieved 1st rank at the beginning by using KHI and LHE, as well as CTU (although I have to admit HKG and PEK were very good as well). KHI, LHE, CTU were no where near the typical mega-airports, but it is not solely about the DOP. You also have to look at your investment. For KHI and LHE, I could use a B737 and fly tons of routes to Europe. CTU is also much closer to Europe than the mega-airports, like HKG, PEK, ICN, HND... etc, so I could use IL's instead of B747/B767's for the long-hauls. The price of the planes count heavily into the business decision. Now, I can tell you that this line up would not work in this round, because of the limitation of the planes but it illustrates the point that being at the largest airports may not be always be the best choice. (But then, if you choose to start at an airport with less than 10 mil pax, you are doomed for sure). It is important to look at the big picture and see what you could do to make the most out of what you have.
Another factor that a lot of junior players have not taken into consideration is how your hubs locate in relation to one another. Are the hubs near to each other or are they all spreadout in different places all around the region? The closer your hubs are located, the easier you could use similar types of planes to fly to the same destination. That increase your efficiency as in you are paying the gate rent anyway, so use the most out of them. You can fly from hub a to destination c, and using the same plane, from hub b to destination c. By using that model, you would be using 2 slots in 1 destination gate, instead of 1 slot each in 2 destination gates.