With decent weather most people make it from
Tampa Bay to the Keys in about 36 hours. The usual routine is to leave late in the day so that one arrives during the daylight. During the winter months, cold fronts can make the trip down a bit rough. You can stay close to the coast and duck in at Sarasota or Ft. Myers if it gets to be too much.
We went from Tampa to the Dry Tortugas, then to Key West and back to Tampa a couple of weeks ago in 8 days. That was with 5 nights under sail and 3 nights at
anchor. The Keys are great if you like the tourist sights, but I preferred the Tortugas for their natural beauty.
Just keep an eye on the weather and try to avoid getting caught out in the gulf when one of those cold fronts come thru.