I've done Marco Island to Dry Tortugas NP at least 12 times. We leave around 4pm and normally arrive 8am. I don't like arriving at dark even though I've anchored there plenty of times, you just never know how crowded it will be. Leaving at 4pm gets you out past the majority of the crap pots before dark, although we've seen a few of them out as far as 50 miles. If sailing, I put the engines in
gear to stop the props from spinning, my thinking is we're less likely to pick up a line.
Radar is your friend when tiptoeing through the shrimp boats at night, we've counted as many as 18 lights visible at one time during one
passage.
If you do want/need to hit Key West, the
wind will usually be on the nose if you run east from DT to KW. We've done that and spent the night in the lee of
Marquesas, which makes for a leisurely
motor into the wind from DT. Next morning it's ~25 miles into KW, allowing you to get there mid-day and no rush. From a wind perspective, you might think about KW first, then a run to DT, then a close haul home.
From Marco, we normally point to the DT NP "I" marker and run the 52 minute line due south into the park. A jog to the west around 'middle ground' and into the NW channel to the anchorage. The channel around the east side of the fort has been open for a couple of years, I've never used it, but the KW
ferry boats used it the last few years.
If you are into snorkeling, be sure to hit 'little africa' on the west side of Loggerhead Key. I normally
anchor in front of the LK
dock in the big sandy area and either
dinghy around LK or
dinghy to the near shore and walk across, depends on the wind/waves. It's ~2.5nm over there from the harbor, so it's doable with a dinghy, but the wind is normally to high. The Windjammer wreck is a good one also, just be aware of possible
current.
Send me a PM and I'll forward the .kmz file of our
route to DT (you can view it with
Google Maps/Earth).