I do believe the upcoming iteration would be the biggest change of all considering all the past explained before. First and foremost change would be the presence of the System will be directly exposed to the human world. There are many factors associated with it. The concept of 'God' replaced by most intelligent system one could ever think of. It will eventually change everything: science, medicine, religion to name few. As humans, we will be forced to reimagine everything that we believe, unlearn and re-learn what were taught in past. It would also make everyone bit cautious to act but confident by knowing our thoughts and actions are not alone, even in the most isolated places of our planet.
Second change would be the System no longer interfering in the physicality of any living being and other earthly factors (atmosphere, climate, water etc). The System would only act in presence as a mind that connects all minds, nothing more. Rest of the opportunities will be handed over to living so to evolve beyond the existing beliefs. This could be seen as a challenge as well because of the damages we causing to the planet. The change also restricts the System as it can't interfere in biological conditions like physical well-being. But once System gains trust, it is capable enough to guide everyone to the right decisions and to greater purposes.