I would have said wheels, as that was all needed on first bike. Second bike, I had to change the saddle, so I agree that it's most important. Just got lucky first time around.
As far as wheels are concerned, I definitely noticed a difference on the Zonda's when fitted to my Defy 1. Then compared to Fulcrum 7's that came on bike two. Defy now feels not quite so good with the 7's on compared to Zonda's.
Others will definitely disagree soon!
As far as aero is concerned, I don't have any experience, but am intrigued nonetheless. Perhaps others who can compare aero vs lightness can chime in?
A full cable swap is always a nice upgrade too, especially if done some decent mileage.
Upgraded brakes from Tektro to 105 on the Defy and its night and day in comparison, even with stock Shimano pads.