I try to stat up villains (and other important NPCs) once the PCs seem close to interacting with them. Sometimes it’s well beforehand, e.g. if they’ve got schemes going on where the type of abilities and skills they have to draw on will influence the nature of those schemes.
How much difference it makes to playing varies between systems, I think. For example, in GURPS and other systems with behavioural traits, the ones you pick naturally flavour how the NPC behaves and their approach to what the PCs do. Does the villain punish failure with death, or encourage learning from mistakes? Will they react with cautious curiousity to a plan’s failure, or double down, or fly into a rage and do something reckless? This can be particularly true if you’re trying to stick to particular point values, and (say) buy a load of expensive disadvantages to help you afford the nifty powers…
This is less the case with D&D-alikes, but there the selection of magic items can significantly shape the options an NPC has available. So sometimes the process of picking abilities and equipment gives me ideas for how an NPC approaches things, and ends up shaping their overall personality.
Do you know if there’s an index to A&E, or at least a list of the ignorable topics? It seems like an interesting set of questions/ideas to browse through.