Just found this thread. I am in Key West at least twice a year, I live about 4.5 hours away. Here are my random thoughts/suggestions:
if you like driving, aren't in a rush the drive down the overseas highway is nice (once) some great restaurants along the way I would recommend the Square Grouper at MM 25
if you want to do the drive, fly into MIA or FLL, rent a car there and leave it in key west and fly out of key west. You do not need a car on the island and the drive back sucks
the ferry from Fort Myers is a good way to go, takes about 3.5-4 hours, during season you can also catch a ferry out of Marco Island. If you go down on a holiday weekend there are often strippers on the boat heading down
strip clubs are hit and miss there, the main ones are Red Garter, bare assets and Teasers
I stay at the Hyatt Centric on Front, mainly because I have tons of points that makes it cheap but there are a wide range of places to stay, if you want to hit Duval I would stay in old town, it may be a little more expensive but you will save on cabs
great breakfast places - two friends, breakfast club too, moon dog cafe
if you are a diver the Vandenberg is a great dive, I use southpoint divers
lunch and dinner I usually just eat at the bar I am currently in, but Hogfish is good - it is actually on Stock Island
you can do the normal bars Sloppy Joes, Irish Kevins, Captain Tony's etc - tons of good entertainers
if you are a microbrew fan, waterfront brewing is pretty good, decent food as well
if you need to kill some time during the day away from the bar and do not want to go out on the water, the Key west cemetery is pretty cool - there are more dead people on the island than living people
if you are hungover, IVs in the keys is awesome, takes about 45 minutes, re-hydrates you and gets rid of 90% of your hangover
Jet ski tour of the island is a good way to see it from the water
If you can get a table outside on the rail at Amigos at night the food is meh, but it is entertaining to watch the drunk people try and throw a quarter in the Grouper's mouth at Captain Tonys
If there is a decent concert at the Ampitheater, it is a great venue, built last year - I saw slightly stoopid, matisyahu and tribal seeds there in June. only draw back was there was not a lot of shade from the sun
They say the only way to get arrested in Key West is to be an asshole or hassle the chickens