I have found that it all depends on:
All three have to come together to get a good fare on a certain day. For ex., in planning our trip to WDW last summer, I spent a good deal of time doing research for flights from each of the local airports available to us—and looking at which day held the best flight times and fares for that day at that airport.
It took me a while, but I finally settled on the airport that worked the best with the airline and the day we preferred to go.
If you only have one way to get there—one airport for departure, and one airline, then it’s pretty cut and dry.
Just as a side note, once upon a time, it was less expensive for us to fly from here to Tampa than Orlando. That didn’t last long however—and when Disney offered ME for free, that saved the car rental so—back to Orlando Int. for us.