Choice of tires/pressure is #1 factor in comfort.

Aero frames typically limit themselves in max tire width, therefore they limit comfort. I run 23c tires, but the rear sometimes scrapes my seat tube.

I bought 25c tires for training but they don't fit my current bike, and I'm having my other frame altered so it won't fit on it (it should fit on the front wheel though). I'm just saving them for now.