RE; isu machinery: I mean, why did humans create VR? :P I kind of theorize it might be a way to "reconnect" the human host with their Isu counterpart (but there's not really textual evidence for this...just spitballing ideas)

As for your other questions, I imagine Lokisim's first few priorities are a) establishing himself into a position of power, or at least ingratiating himself to the modern day assassins b) getting Aletheia a body and c) finding his children who may or may not have been reincarnated or preserved in some way (to be revealed in later games or DLC, I'd imagine). It's unclear to me if the other Isu were able to repeatedly transfer hosts or if Eivor, Sigurd and Basim were one-off reincarnations.

Aletheia is Angrboda, yes. Not sure about how much she was manipulating Layla in order to be with Loki again vs just trying to get Layla to fulfill her role as the heir of memories.