We had an '02 and my parents still have a 2000. Prior to the 2000, they had a '98. They are great vehicles mechanically, however they do have some issues, many of which are shared with the same vintage F-150 upon which they are mostly based:
1. Front suspension bits. They are hard on tie-rod ends and upper/lower balljoints. The Moog replacements seem to hold up well.
2. Exhaust manifold studs breaking off and leaking. Sounds like you've already got this going on. There are updated stainless studs available. It is usually the right side that fails.
3. The PI-headed versions of the 4.6L/5.4L had a tendency to launch spark plugs, particularly after the threads were damaged by the plugs being changed. This is not an issue with yours IIRC.
4. Rear axle seals on the 9.75" rear-end once the miles get on it. Both the '02 and the '00 have had these replaced.
5. The rear trailing arms can, in areas of heavy road salt usage, rot out.
6. The trans cooler lines can rot out (this happened to the '02)
7. The sunroof drains will back up and rot out the rockers (happened to the '02) from the inside
8. The rear parking brake cables will seize. So will the integrated rotor/drum parking brake assembly
9. The ABS controller dying, causing the pump to run constantly and killing the battery
10. The main power lead for the starter, the end will rot off.
And of course minor stuff:
- Coils failing but not setting a fault code
- The DTRL resister pooping the bed
- The heated drivers seat will fail
As you noticed, with rear HVAC, some of the coils are a monumental PITA to change. The plugs are worse. they 6" down the tube and on an angle. Take your time.
If the power steering is groaning a few drain/fills with M1 ATF or AMSOIL ATF will greatly reduce it or eliminate it.
The 4R100 transmission is close to invincible in this application (was designed to be behind the 7.3L PSD), as is the 9.75" rear-end. The front is also a very robust 8.8". We never had any drivetrain problems with either of them. Both are still on the road, I sold the '02 a couple of years back and the guy was going to drive it for the winter. Found out how good it was and it has been his DD since. Likely has around 200K miles on it now, as it had over 180K when I sold it. The 2000 has similar mileage.
They are pigs on gas and there's no way of helping that. It's a 240HP (in your case) V8 moving a 6,000lb behemoth mated to a massive antiquated 4-speed, which is in turn mated to a large BW transfer case with a clutched engagement mechanism for the front wheels, with two driveshafts that are always turning. It will pull the proverbial pooper out of the world in 4-LO and we had no issues doing extensive towing with both of them.
All-in-all, it got us through numerous ice storms, deep snow, pulled guys out that got stuck and generally was just a fantastic vehicle that really liked fuel. I was not easy on it, and it never left us stranded.