Any of the Extangs offer a reasonably secure option. Some are held on with clamps so you can take it off in 5 sec without any tools. When it comes time to pull the fiver, Stow it away in the trailer and reinstall it after you unhook. Most of them fold as thirds or fourths.
I went with the BakFlip on mine. I haven't towed the 5th wheel yet, but whether the cover is flipped to the last section, or if I have to flip it all the way up, it will still work. What I mean above is, when you flip the BakFlip all the way open, it actually leans against the back window, effectively blocking your view out the rear window. Which with the 5th wheel behind you, it's not really a big deal, just a little weird getting used to. But I think it will even work with one panel still down.
I had a Extang hard cover before on my 8' bed, and I really liked it, but I don't know if the 6.5' would have worked, since it only has 3 panels.
As far as security, none will be terribly hard to break into, but will keep the honest thief out. And with the hard covers, you can walk on them (I'm close to 250 pounds and can walk on both my BakFlip and the Extang with no worries).
I went with the big bucks and put a Roll 'n Lock Electric on my 450. I have the factory 25K fifth wheel hitch and I use a bungi cord on the handle to tilt the hitch to the left so it won't interfere with the bedcover. It has aluminum slats under the black cover, so it might take a little more than a sharp knife to get in.
I have the BakFlip G2. The cover itself does not lock (with a key), but is locked to the rail attached to the bed frame. Locking the tailgate is what provides the security. Again, it wouldn't take too much (I suspect a good tug or 3 with a crowbar) to get in, but it will keep most people away.
You open the sections with the pull of a wire cable. The cable is available on both sides (so you can open the cover from driver or passenger side...nice). The first panel is locked, the second is not locked, and the third and fourth are locked (each requiring you to pull the cable to open the panel). When you open it all the way, as I said, the open panels will rest against the cab of the truck and windshield. But the cover comes with rubber "bumpers" to protect the cab/windshield. And there are two "stabilizer" bars to hold it all very tight. Overall I am happy with the cover, especially for the price.
Be sure and look on E-bay for the cover. You'll see lots of them. I found one on there with free shipping and the considerably less than any of the local stores around here. And better yet, since the place I picked on E-bay was based out of Houston, it was here the next day. What a deal! In fact, I need to go back and commend that dealer.
How much room does the cover occupy when folded all the way against the cab? I have a truck box that sits on the floor and would sit under the cover just fine, but I'm trying to figure out if there is enough room to still situate the box back some and open the lid enough to make it useable still.
Pearl, my set-up is almost exactly like yours. I've got an Extang rollup cover that sits nicely up against the front of the bed when rolled up and clears my hitch lever by an inch or so when pulled taught. My clearance had to be 18" to cover the hitch lever and it just makes it. My in bed toolbox stays away from the front of the bed with a 2X6 up against the bed front wall. The whole setup is great and with the cover stretched out, it hides my hitch nicely.
I'm running a goose, so hitch overhead clearance is not an issue. The toolbox sits below the rails, so also will clear fine. I've considered the roll-ups. Is yours one that is like a roll-up garage door w/ a box it retracts into? If so, how large is the box. By what you wrote, I'm guessing it is only about 6 inches wide from the headwall. My brother had a similar roll top, of what brand I'm not sure, but the box was 10-12 inches from my recollection. That would waste way too much space in front of the toolbox. Does your roll-top leak or do the rails contain and drain the water?