I did the entire NT once (and the section from Anacortes to Glacier N.P. a second time) and the TA between Missoula, MT and Fairplay, CO (on the downslope of the last mountain pass in the rockies).
One consideration is that you will have more (and higher) western mountains to cross on the TA. On the NT there are really only 4 in WA and 2 in MT/Canada. In the stretch of the TA between Missoula, MT and W. Yellowstone alone there 4 or 5 depending on how you count them. You will later get to 9,600 on Togwotee Pass and ultimately to 11,500 outside of Breckenridge. (The good thing about that climb is that Breckenridge sits at 9,600 ft. so if you start from there you only have to climb about 2,000 ft.)
And while I have never ridden in KY or VA, being from PA and knowing what I know about the Appalachains, I cannot imagine that they are less rigorous than the Adirondaks of NY and the Green Mountains and White Mountains of VT and NH, respectively.
As for safety, on either route you are going to find places where the riding is less than optimal. I hated some stretches in CO. Yellowstone had its dangerous moments as well. But so did MN and OH. Overall, I felt less threatened than I do when I ride around home.
I chose the NT for my x-country tour because I had never done any loaded touring and had never slept in a tent in my life and thus was worried about taking on too much. But knowing what I know now and having ridden some of the TA, I would have rather done the TA. It's the Grand Daddy of them all. If you opt for the NT feel free to send me a personal message if you have any specific questions.