There's issues of brake clearance, and clearance between the stays and behind the seat tube. Measure and see how much additional room you have.
Additionally, there's the question of rim width. Some rims, particularly aero-type racing rims, have an inside width of 13mm and really can't take much more than a 25c clincher. You might be able to get a bigger tire on there, but running too big a tire on narrow rims risks sidewall damage and handling problems. You can often get a recommended range of tire sizes from the rim manufacturer.
You're right that running the fattest tires you can fit will help guard against impact damage from potholes (but not as much as avoiding the potholes will!), but it's the amount of volume in the tire and the sidewall depth and stiffness, not the presence of knobby tread, that will do the job. A 700x28c touring tire, if it will fit, would probably be a good compromise.
Training: 2002 Fuji Roubaix Pro (105 triple)
Commuting/Daytripping: 2001 Airborne Carpe Diem (Ultegra/XTR, touring wheels)
Commuting/Touring: 2000 Novara Randonee (Sora/Tiagra/LX, fenders, lights)