Tires, saddle, and shoes are larger determinents of overall comfort on long rides then frame material or geometry assuming proper fit. For me.....getting big tires AND fenders was the key criteria for frame selection.

I recently went thru the decision process of what frame to get. Fitting fenders and wide tires was the hardest requirement to meet or maybe I did not do enough research. I ended up buying a used cycle-cross frame with a long wheelbase and wide stays that can take tires as wide as I want with fenders if needed. There really are not many off the shelf frames or suitable road bikes that meet that requirement unless one spends a lot of money. The Specialized Roubaix or Trek Domaine cannot mount 28mm tires and fenders, which render both useless to me. I wanted carbon and bought a Trek Ultimate CX frame and mounted the parts up on it. Just need to buy a cyclecomputer and a set of fenders.