From Tampa, I would do I75, off to 41 just before Alligator Alley, take a right on Krome Ave.(997) all the way to US1.
Keep in mind, 41 is a 2 lane road and if there is a wreck it get's backed up pretty bad. I have only had that happen once though out of 14 trips.
BTW....when you get into The Keys, if the speed limit is 45....go 45. They don't play down there.