I have a '98 Cannondale Silk Path 300.
I've used it for a mix of on- and light off-road use (not surprisingly, considering it's a hybrid); most of what I've used it for the past couple of years has been largely road of varying conditions, though I haven't given up on unpaved trails.
It currently has 700x38c tires that I'm looking to replace; the sets I've been considering (Schwalbe Marathon Supremes) run either 700x35c or 700x40c. I've considered going for the 35c's, mainly because I'm having an easier time finding them. The slightly lower rolling resistance over the 40c's will be nice, but am I giving up long distance comfort? Or is the difference too slight?