I have used both Airline Mogul and AirwaySim (both mentioned above)
I find AirwaySim to be far superior. It has (very nearly) every commercial airport on earth programmed in (4500 and counting), as opposed to the ~2000 on Airline Mogul. AirwaySim has an extremely intuitive route scheduling and planning interface, that allows you to manage as much or as little as you like, with fancy graphs and visualizations that closely reflect reality. AWS also simulates reality closely while not exactly imitating it - fuel prices follow general trends (but random spikes are programmed in) and aircraft launch dates are randomized within +/- 18 months so no one airline has an advantage. The only downside to AirwaySim is that it costs ~$1 per week of game play for the full game worlds. But it is well worth it.
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