Everyone has really nailed this one. O&D is key. It also has to be quality O&D. The non-hub cities out there that have international service are either in the same region as that city, have plenty of tourism traffic, or have a lot of high paying industries.

Examples would be...the Northeast and Great Lakes that have flights to Toronto or Montreal simply because it is like another regional hub for traveling.

Tourism flights...look at what Frontier is doing on all their flights to Mexico from random cities in their network.

The last example would be non-hubs like Raliegh-Durham that have nonstop flights to cities like London due to their local industries...banking and R&D being RDU's big one.

Customs aren't as big of a deal as they use to be. For the cities OKC would target...in Canada, Mexico, etc....the growth of Pre-clearance services (going through US customers in those international cities before boarding) will help this out. Toronto is one of those cities. Cancun is suppose to be getting it soon.