Dont need to remove the wheel well, and it won't give you that much more room. Just jack the truck up to make room for your gut under the truck, wiggle your booty into position and use an open ended box wrench or adjustable wrench to unscrew it. Fairly simple, but your right it isn't super easy (like a lug nut) but its also not extremely difficult. Good luck...
try hitting it with some penetrant lube while it's hot, preferably the non-flammable type. then let it cool off so ya don't leave charred skin on the pipe. the lube may make it easier to get off with a normal length open wrench. All my experience with O2s involved a 2ft breaker bar and they still put up a good fight. Put some antisieze lube on the new one before installing.
I can vouch for it being a pain in the ass. I just replace both sensors on my '02 4.7L as part of preventative maintenance.
I was lucky that I didn't need a breaker bar to remove them. The one after the cat is easy to do, so you might want to unhook the connector on that one just to know what to expect for the sensor before the cat.
I thought about removing the wheel liner but in the end it probably would have taken longer to do that then lay and fight with it.
As a tip, use a screwdriver or nedle nose pliersw to push down the tab. My forearm wouldn't fit all the way between the exhaust pipe and tranny to reach the connector, but I could easily push the tab using a screwdriver. It helped to also push the connector in before pushing down on the tab before pulling on the connector.