I've run with an open bed, hard tonneau cover and a topper (cap, shell, etc). First off, I'll say no matter which option you go with, the load is going to be secured essentially the same way. Just because you have it covered, doesn't mean you can just toss everything in the back and head off down the trail.
Open the obvious issues is weather and security. Yeah, you can still sleep in the bed, but it's weather dependent. Also, all of your stuff has to be weatherproof. This is not my first choice. True that even with a topper or a tonneau cover, it's still fairly easy to break in, some are better than others (DiamondBack).
I then switched to a Ridgelander Overlander tonneau cover. This is a rigid cover that also has a Rhino Rack built in. It was great for keeping the weather out. It's not watertight, in fact you'll have to do your own mods to make any bed cover watertight. Loading and unloading was a real PITA up near the bed. You get really tired of crouching down to access everything. You are also limited on the height of everything you carry. You have to be really picky on which storage boxes, refrigerators, etc. that you carry. The pro is the lower overall height of the truck bed. I've been in situations where I was able to get the cab past an obstacle, only to have the truck shift or the angle make it so a topper would hit the obstacle. As for sleeping in the bed, again you are limited to the weather. I suppose you could sleep with the cover closed, just feel claustrophobic to me. I did have one thought of adding tent-like material to the sides of the cover so that when it was open, it would almost be like a hard-shell roof top tent.
I currently use an ATC topper which includes a Rhino Rack roof rack with a 500-pound capacity. I have plenty of room. I like that I have windows that can open for ventilation. I've got lighting built-in and insulation on the roof and sides. A sliding window still gives me a little access to the cab. The biggest pro is that I'm not limited on the height of the gear that I carry. Obviously height is also a con, as I mentioned above. You really have to think about your line and placement so you don't damage it on the trail. While they do come off fairly easy, it does make it more difficult to use your truck as a truck (also true with tonneau covers.) My only regret is that I wish I had went with side windows that hinge open from the outside (windoors). This would make it was for me to access stuff towards the front and side of the bed without opening the back (maybe even a little rain protection).
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