The problem starting in these smaller 'second tier' airports used to be the out-of-base limit, which would hold back the size of your airline later, as there is never really the demand to have maga-numbers of a/c at home base. This is somewhat less of a concern now that the limit has been increased but it might still block your growth until later into the game.
I'd be tempted to start up at a large hub (somewhere like ORD or LAX) and then jump to one of these smaller airports as soon as possible (is it six months now?). You can grab a lot of the 'cash-cow' routes at HQ before the initial slots run out and then concentrate on mid-sized airport for 30 or 40 years while your competitors fight out the bloodbath over non-existent slots and oversupply at the big airport. You'll be able to continue growing steadily while they are hopefully tied up in a battle of attrition - there's no point being part of that. Then, later in the game when you've maxed out your out-of-base limit, with say 100 a/c at each of 4 or 5 smaller airports (or as and when you periodically hit that limit), you can jump back into the big hub, which will now have plenty of slots and only one or two big airlines. You'll have a large fleet of profitable mid-size narrow-bodies and maybe a load of turboprops and you'll be able to drop literally 100s of a/c onto routes at your HQ and hammer the larger guy on frequency. I think that's the quickest and least risky way to build up a 1500+ a/c airline in the US under current game rules.
With the addition of cargo, this strategy should work even better, although I'm yet to actually try it. Choose the secondary airports for their cargo viability (ideally in isolation and not overlapping a large hub) and you should have a stead stream of uncontested income throughout the whole game. Secondary airports in large urban areas, such as LGA, BWI, SJC, ONT, HOU, DAL, FLL etc. were always good possibilities but are improved by the fact that you can 'steal' a good proportion of the cargo from the nearby hubs. Places like BNA, MEM, OKC, MSY, IND, SMF etc. were always a bit limiting for pax. alone, but have good cargo demand that is not shared with a nearby mega-hub.