At ASA we fly CRJ-700s into EYW. It's special due to our Op Specs. Captains must make all takeoffs and landings and must be route qualified. A check airman takes each captain there during IOE.
As to why its special, let's think about it for a minute:
Very short runway by airline standards (4900ft).
Military base and restricted airspace within two miles of the approach.
Extremely heavy traffic conjestion, mostly VFR.
Tethered balloon to 15,000' within two miles.
Strict noise abatement.
Lack of a good instrument approach.
Surrounded by water.
Tight taxiways.
Etc...
What's funny is that ASA flies CRJ-200s into APF (Naples, FL) which has a 5000 foot runway. If you don't know, the takeoff and landing performance of the -200 is about half that of the -700 due to the -200 not having slats. There are no restrictions except to power back to 79% for noise abatement. I don't see how 100 of runway can make all the difference, so EYW must be restricted due to the other stuff.