I'm currently running 285 BFGs on OEM Pro wheels and so are lots of others and they're fine. I've got about 3" of lift in the front and I'm also running SPC UCAs and spidertrax 1.25" spacers. I trimmed the front bumper and pushed the liner forward and did a BMC due to the rubbing, which I believe the spacers caused or at least made worse. Lesson is, you might rub because every truck's setup is different, and if you do, be prepared to trim the bumper/liner and do a BMC. If you want to avoid the possibility of doing any of that, stick with 275.
The middle of the tire wearing faster than the outer tread has more to do with your tire pressure. If that happens your pressure is too high. If the outer tread wears faster than the inner tread, your pressure is too low. BEST way to figure out the correct pressure for your tires is the chalk test. Google it if you don't know what that is.
You shouldn't need to worry about losing a bead. I've aired down to 15-16 psi and have been fine on some pretty intense terrain. I mostly stick to 18-20 psi though as that's what works for my tire/weight setup. My KO2s are load range C so the sidewalls aren't as stiff as load range E. I only have to air down to 18-20 psi depending on my weight to get a softer ride and decent tire bulge. Load range E you have to air down lower for the same ride quality due to the stiffer tire. Load range E at the same pressure as load range C won't bulge as much and will be stiffer but can support more weight. And of course there's the increase in puncture resistance, but I haven't had any problems with load range C and I've put them through the ringer.
And yes the spare will fit in the OEM location. 285 size or about 33" is probably the largest you'll fit under there especially if you have KDSS. It will touch the sway bar but it will fit. I haven't had any problems with mine.