What a coincidence....
I also have a 2000 XLT w/4.6, and was plagued with the same problem. I had the check engine light come on, so I took it to the local "trusted" mechanic. He ran the codes and it came up that my #1 cylinder was misfiring. We changed the coil pack, and that helped for about 10 minutes. Next, he thoroughly cleaned out the EGR Valve and determined that I needed a new one. So we replaced that. The check engine light was reset, and off I went. Ran great.........so I thought.
Two months down the road, my Expy started misfiring again. So back to the "trusted" mechanic I went. This time they read the codes and said that the #6 cylinder was misfiring. So we replaced the coil pack there, reset the check engine light and off I went again. Ran great...............for about 2 miles. I immediately drove it back to the mechanic and he quoted me $1000 to replace the other 6 coil packs, that he stated, "would go bad one after the other". I just about sh*t myself. I asked for my keys and left the premises with a poorly running vehicle that I had already spent nearly $1000 to fix just two coil packs and an EGR Valve. I went to the local auto parts store, spent $400 got the rest of the coil packs and changed them myself. Turns out that you only have to unscrew 1 screw and unplug one plug to get them off and then repeat the process backwards to install the new one. Takes about a minute and a half to do, and I was being charged $180 labor for each one. I guess I am in the wrong business. I would love to make $180 every minute and a half!
Due to this scary experience with a "trusted" mechanic, I prefer to read manuals and do it myself or take it to a dealership (and sometimes you can't trust them either). It is apparent that this is a common problem.
So far so good, I haven't had any more issues since this and I just recently upgraded my exhaust system to a Flowmaster 50? series. It has a nice low rumble at idle and deep throaty sound under load. I love it and it may have increased my gas mileage by one or two gallons too.
Good luck with your Expy!