I thought this would be an interesting topic to bring up, seeing that there's a large variety of approaches and themes behind the airlines of this game.
Personally most of my airlines tend to be mainline, transatlantic airlines operating from large-medium hubs, although I throw a number of other airlines in the mix. A majority of my airlines are set at airports with locational limits (Dynasty Pacific and Macau Pacific at HKG and MFM, Aquarius Tahiti at PPT, FijiAir at NAN, Greenlandfly at SFJ, etc.) or political limits (Formosair at TPE, Al Israel at TLV, Cubavia at HAV).
I run my airlines in a sort of "AElism", I set up flights from my hubs (which usually number no more than 3) to all the airports that could be realistically served in a reasonable distance. The fleet types tend to be streamlined with realistic/semi-realistic seating configs, and I use fleet types that some real airline in the country my airline is based in has used some time in the past or present. I tend to set flights in factors of 7 for organization (unless they're at a very small airport), and really don't worry about utilization times, but don't try to squeeze every hour out of my planes.
What are your thoughts, how do you run your airlines and what kind do you use?