Flying into Miami, renting a minivan (hey, four girls = lots of stuff) and driving down the coast and through the keys is well worth it. It's cheaper than flying directly to Key West, it's a scenic drive with lots of neat places to stop, and you get to have a short "car vacation" which always yield more memories than a plane ride! :)
Hemingway's house is a must! I'm not an avid reader, but the guides also offer insite into a little Key West history, which was cool. The house itself is neat also.
There are lots of bars and clubs on Duval. We made it a point to try and visit all of them. They each have their highlights, and I recommend at least trying a few!
The weather in Key West is awesome! We began to wonder if it ever rains! A local assured us that it does, but rarely. I think he's lying because all the restaurants, bars, clubs, and many shops are open air with decks and outside patios. We only saw a few clouds during our entire stay!
Quick Tips:
Ask for locals suggestions for cheap places to eat - eating in KW is not cheap, but the locals have to eat somewhere!
Key West is famous for their sunsets and yes, you have to see one from Mallory Square. BUT, another (less-crowded) location is from the tallest building IN Old Town, The La Concha Hotel. It's on Duval, only 6 stories tall, but it's a great view of the sunset and the town.
A great thing about Key West restaurants: There is almost never a wait! We would never eat till 7 or 8, and where I'm from, this would mean waiting for an hour. Not in Key West! We were always seated promptly. (with the exception of our 20 minute wait at Hard Rock Cafe).
Best Way To Get Around:
Mopeds, bikes, and walking are the best ways to get around.
We had rented a car to get down there, but then returned it to the airport. Our 3 mile cab ride for the 4 of us? !! It was per person! As for having a car, there is nowhere to park near the main drag (Duval). Most of the parking on the streets near it is reserved for residents. There is no parking on Duval, and none of the restaurants have parking. There is a parking garage at one end (by Mallory Square), but I'm not sure how much it costs. Most everyone on the island is on mopeds (~/hour, /day, /week), bikes (/day, /week), Harleys (for which there is parking), little moped-engine cars (~/day i think), or just cruising in their convertibles on Duval (and not parking).
We rented bikes. They were great, but we were only a few blocks from the beach and half a block off Duval (easy walking distance). We enjoyed the exercise and the fun of renting the bikes.