I did not enjoy the trip from Islamorada to Marathon on the inside, pretty as it was; too skinny and way too many crab/lobster pots in the channel. While we didn't run aground per se, we sanded the keel pretty nicely. You're not going to hear many rave reviews of that stretch from people with more than 4 feet of draft. From Key West to Marathon, you can anchor in Newfound Harbor and Bahia Honda and have tons of fun on the dinghy exploring the inside.
On the other hand we really enjoy cruising on the inside from Channel 5 east/north. Lingnumvitae Key, Shell Key, Matecumbe Bight (Islamorada), Tarpon Basin, Pumpkin Key (Ocean Reef), Elliot Key are all favorite anchorages or moorings. I haven't been there myself, but people speak highly of Plantation Key as a marina destination.
As of two weeks ago, Anglefish was not an issue for us with 5 feet at all, just mind the channel and take your time (so what else is new?).
George