While personally as a pnwer I prefer NY-Cleveland-Chicago-Minneapolis-Seattle, and I do think that that's a route you likely eventually want if for no other reason than to hit the Dakotas and North Yellowstone, going south of Yellowstone means that you have major cities between the Midwest and the coast, namely Denver and Salt Lake City.

Ultimately I suspect the best option for the spines is something inspired by the interstate with 3 E-W lines, probably aiming for Charleston-San Diego on the south, DC to San Francisco in the middle and NYC to Seattle in the north. But it would require enough commitment to ensure that it actually gets built that way, otherwise it's better to make something worse in the long run that's never in an awkward middle stage where it's not good enough to defend.

That really gets to the core of what I think the problem is. Our country is unable to commit to improving anything when it gets hard. Some parts of it can, I used sound transit as an example in my first comment in part because it specifically is a very young transportation network, originally being approved only 30 years ago or so. But rail networks are long term expensive projects to build and while the government could throw war amounts of money at it, it's highly unlikely. Our best chance is one or two pilot lines that take a decade or so and then us pushing for more and more. That said, if we have an economic depression this could be a part of the way out of it akin to the ccc was in the new deal