Eric,
I agree with you that the backpack will be more practical and manageable. Most areas you will visit don't really require a whole lot of walking. You'll be standing most of the time in reality. If you're going to visit Ft. DeSoto then you definitively don't want wheels on the beach. In fact, you'll probably end up on your knees shooting shore birds and get your legs wet as you wade through the shallow water. The wheels won't like that!

I have the thintank hard drive and I can even fit my 800mm with the 1dx body and the 100-400 L. It's a little tighter than I'd like, but I've done 5 to 8 mile hikes with this and my induro CT314 and gimbal head. I'm pretty much dead at the end of the trip, but it is possible, and I definitively don't consider myself to be in great shape :)

Though I am sure many have done it and suffered no major issues, I would recommend against leaving valuable equipment in your car when you park. I've done it many times, but if you can carry your stuff you'll know where it is at all times.