I am an avid runner and there are many things you can do to keep you comfortable during a run.
First, even though your shoes might be comfortable, you still might be wearing the wrong shoe for your foot or even the wrong size. Typically, you are suppose to wear one size larger than your typical shoe size in running shoes. Your feet swell why running. I suggest going to Fleet Feet or Lukes Locker to get fitted properly for a running shoe.
Second, cotton socks can cause blisters. You should be wearing some type of wicking sock. I love the socks at REI. They are for cycling but I like them because they are not boring white.
Third, to prevent chafing and blistering in other areas or on your feet, you should get a product called Body Glide. It looks like deodarant. I put this on my thighs and sometimes under my arms if my shirt is rubbing. You can get this at any running store and I think you can find it at Academy.