So much is personal preference so it is hard to make recommendations.
An acquaintance who rode all of them, most more than once, said his favorite was the Southern Tier. I liked the food and the people, but found the scenery mostly underwhelming. Others liked it better. For me the biggest reason I'd ride it again is because it is available in the winter (I rode it San Diego to Pensacola in mid Feb to mid Mar). It was fun to meet and hang out with the endless stream of misfits who were almost all transplants who didn't fit in somewhere else. Also there was food... Tex-Mex, Cajun, gulf seafood, good old southern cooking, barbeque and so on. Still, It was a long grind with brown nothingness day after day way too much of the time for me.
I really enjoyed the Pacific Coast, at least the portion I rode (Seattle to San Luis Obispo). I'll probably do it again multiple time in my life at least in chunks, especially Oregon and Northern California. The problem is that there is a very awkward detour due to a mud slide near Big Sur that washed out the road. These can take a long time to repair and the detours can take you away from the coast for 100+ miles of the most select part of the coast. They seem to occur somewhere on the California coast every several years
The portion if the Sierra Cascades that I rode (San Diego to Reno) was stunningly beautiful, but also exceedingly difficult. The climbing was insane.
Maybe it is because I lived there my whole life, but riding the Atlantic coast sounds pretty unappealing to me. There are sections that sound nice, but a lot of it sounds like it would suck IMO.