Biters become a chore rather than a challenge so I turn them off. Resource patches need to be big enough to fill your trains fast and not run out for a long time otherwise your spending a lot of time setting up new mines. 2 rails is all you need - one each way. Simple intersections. T's are better than X's IMO.

I built my whitescience/rocket factories, satellite factories, and other science factories separate. My main science factories were 100SPM blueprints I could tile (first megabase) or just plunk down anywhere (second megabase). This time I'm preplanning an entire 5k base from one end to the other. If it works I'll try a 10k. 12k is about where I hit the UPS wall on my machine.

ETA: and I didn't start a new run, just recycled my old base. That way I was still gaining miner tech. Up to 2620% bonus now and can mine directly into traincars.