I'm pretty comfortable with blisters. They are always present to some degree and prevention of monster blisters is my main focus now. Small blisters share a thin line with good calluses. I have a few nuggets of wisdom to share on the subject that I've obtained through trial and error:
Run with dry feet-if I slap on my Vibrams immediately after wearing suffocating, sweaty shoes all day, I'm guaranteed to get mega blisters. Same with running barefoot-giving my feet time to dry out after wearing shoes for the man makes all the difference.
Wear socks-long runs always remind me where my feet rub the insides of my FiveFingers. For this reason, Injinji socks are usually necessary for me above the 5K range.
Separate toes-my toes used to rub together, causing blisters inbetween toes and on my toe joints. This is not an issue with barefoot running, Vibrams, and with Injinji socks in any shoe, I imagine.
Don't mess with blisters-Don't cut open blisters. Don't cut them off. Just leave them alone. It's worse if you filet them.