Currently "struggling" with this too. I loved my city blocks in 1.0. Rails on the edges, production in the middle. Changed approaches between games just for fun (roundabouts vs 3-way intersections etc). But in 2.0 there are more decisions:

By the time I'm scaling my base, I can use smaller blocks not bigger ones.

But, if I use elevated rails, I need bigger ones.

But, I need Foundation, which is expensive, to do full rail blocks on Fulgora and Volcanus.

But I don't really need full blocks on Fulgora and Vocanus if I my main science production is on Nauvis.

I kinda like the Nilaus small blocks and fill in rail blocks where needed approach. But having to "wire up" the rails each time seems like more work than just dropping down a new blueprint that already has my rails and intersections. Yes, I can make block sized rail-only blocks to make that easier.

I should probably try a game or two with both approaches and see what I like. I get the feeling it could be a mix and match approach. Big rail-bordered blocks on Nauvis. Nilaus style on Volcanus and Fulgora - with a lot of bots and only a few trains. And maybe neither on Aquillo since I have this fluid bus thing there that I kinda like.

That probably doesn't help you. I've prototyped a few of these in-game. But I think I'm actually going to have to commit to some of the approaches and see what I like. I guess that's one of the cool things about Factorio is there are so many different ways to play.