I've got my exhaust manifolds off and fixing to have them Jet-Hot coated. One of them has a small, approx .5" diameter hole at the back that has a little heavy steel cover bolted over it- I'm assuming it was some type of egr related port. I'm wondering if I can take that cover off and just weld a plug in with my wire welder, or could it potentially cause cracking problems? Jet-Hot says they can probably coat the manifold with the bolt on cover in place, so I actually don't have to do anything...

I'd probably just tap it & put a plug in it. I've arc welded manifolds with special rod in the past, just bolted manifold to an old head & preheated to 350 degrees. Always seemed to work, at least as long as I owned the cars/tractors. Never tried wire feed, though.

Is cast iron very difficult to tap? My thinking is that if I leave that cover in place and they coat over it, then that seam becomes a potential rust/failure point for the coating...

No, it threads quite easily. If there's no gasket between the plate & manifold, it should be fine after coating it, I would guess. I just thought it might look a little cleaner without the plate but maybe you can't even see it with the motor in the car.