To answer the OP's question, the bigger airports 300k+ airports in Europe and North America will yield the most if you can maintain your routes. If you find other regions interesting and you don't really have to live there lol, they can still be profitable if you choose your airports wisely, you also might want to consider acquiring a large foreign base to greatly boost your income in the smaller regions. As for me, I live in the outskirts of NYC, but I tend to base on continents outside where I already live. The fun factor comes in playing a region not many will base at and try to do well on it and pull that continent 'up' among the 1st class continents.
When I played in Central America in one of the Full World map in a public world, I started out in Mexico city as Aeromexico then chose a nearby large foreign base in Houston as my second focus city. Also played Africa twice as South African Airways, I chose ORLY and MUC for my foreign focus city and the rest are African airports. They all increased the airline value tremendously. If you want to make all your hubs local, that's fine too, just pick the big ones and ones with lots of airports in the area. If all else fails, pick whatever region appeals to you at that moment