I've more or less given up on playing to win in AE, so instead I'm having fun by playing with themed airlines. Gives it a bit more structure so I'm not constantly expanding, nor do I feel the urge to.
For example, my S4E run was Disney Skylines, with MCO and SNA as my hubs. Then I tried my hand at running Porter Airlines out of YTZ in S4B. And now, I've got two airlines in O1 representing the two halves of Major League Baseball (plus their farm teams and international counterparts). Next up I'll probably do a single O1 or O2 run for the National Hockey League teams.
What have you played around with that turned out to be fun? I'm tempted to do a Sandbox playthrough with all-double-deckers or all-Concordes, or going as green as possible.