The 3rd science pack is probably the hardest leap forward. But purple/yellow science are difficult too (just not “as hard” as blue IMO).
The 3rd science pack requires mastery of oil refining. The 4th and 5th (purple/yellow) science packs are “just” about scaling up to exceptionally large bases, which is easier IMO than trying to figure out oil (though still somewhat difficult, and the scaling is of two grossly different stuffs. Purple science requires a ton of stone-and-steel, while yellow science requires a ton of copper).
Once you recognize that purple and yellow need way more space than you originally expected, its actually really easy. Just build “bigger” than you ever had before, but otherwise the basics are the exact same as red/green science. Don’t build a “few” assembly machines, you need to be thinking of at least 50+ assembly machines for the entire purple / yellow chains, and possibly need ~2 or ~3 belts of raw iron ore (for purple) or ~2-to-3 belts of raw copper ore (for yellow). Meaning you need maybe 200+ furnaces (I’m not joking). But… “big designs” are just big, they’re not actually difficult to think about.
3rd / Blue science is difficult because its the only time you ever have to master fluids in Factorio. Fluid trains, fluid wagons, fluid containers, etc. etc. You pretty much have two designs: you either bottle everything up into steel drums so that you can “stick with belts”, or you learn to properly use pumps+pipes+trains (fluid wagons) to move things around. In both cases, its complex but its the only way you get past blue-science.