The difference is The Severity of time, Hashirama's era was all about child evolution as opposed to Shishu/Itachi era(Minato exempt because he was the Chosen One) which was deluded/Weaken due to the leadership of inferior Men like Hiruzen/Oonoki= selfish Men who had no intent on passing down their anicent ninjutsu out of fear of growth beyond them = Oonoki descent didn't know how to fly or Particle Style, Hiruzen didn't pass many of his Skills to Asuma if he did he wouldn't have died to a Akatski member while quadruple teaming him. Itachi's had a sense of resolve thats why it was easy for him to think outside of the box to do what needed to be done thus evolving while his generation was weak because Hiruzen taught them how to be stagnant and also to admire the present power instead of seek it and evolve, example: During Hiruzen rein Just look at how proud and happy a genin was to beat up younger children instead of compete with older ones in attempt to surpass them such as Izuna and Madara, Sasuke , only people that evolved were people who lived away from their Kage or didn't admire/nut hug them such as Kimimaro, Itachi, Sasuke, Shisui, Hiku, Gaara, and those are just a few reasons.