The area on the west side of the lake where the channel makes turns is problematic if you vary outside of the channel. I have never had a problem but have been told do not let the boat "wander" in this stretch and heard of groundings.
This can be challenging if you leave Clewiston in the early morning continuing east. You have the sun over the lake directly in front of you. It's worth having someone helping watch the markers and location.
The other area (if you have a deeper draft) is in the St. Lucie river just east of the bridge before you get to Sunset Marina. In our previous boat we would run the lake in 1 day. With our current boat (deeper draft), we time our crossing to go through this area at high tide. Almost always a 2 day trip now due to timing.