Key lime pie is my favorite dessert, and I decided I would try it every place I went where it was on the menu. Unfortunately, this was about seven years ago and I don't remember who had the best! Kermit's was good... but honestly, so is the Publix key lime pie. I'm pretty sure I tried about 15 different key lime pies that week (with only two full days in Key West; the rest was split between Orlando and the West Palm area.) With a shellfish allergy, I was very limited in menu choices in the Keys, so I justified all the pie.
Someone mentioned Danger Charters- we also did an outing with them. We did a snorkeling trip and really enjoyed it. Don't miss the sunset celebration in Mallory Square, and give yourselves some time to just walk around. Some of our party toured Hemingway's house and enjoyed that (I did not go, I was probably looking for more key lime pie.)
On the way down, I highly recommend a stop at Robert Is Here, a... well, farm stand isn't the right word, but maybe a cross between a farm stand and market and petting zoo? We ended up stopping on the way down and on the way back up- I think it's in Homestead. They have a wide array of milkshake flavors, tons of local fresh fruit, and animals out back.
On the way back, we stopped at the state park in Key Largo for a glass bottom boat ride- it was nice, but we didn't see too much (always enjoy a boat ride, though!)