I think the Aztecs will be much like Egypt in RTW: it's sheer mass will present you with the most difficulty. Aztecs and Incas had for the most part a strong economy, combined with eager armies.
There will probably be some scripting included to partly recreate history, such as the social turmoil and a few plagues now and then. Also their units will be a lot cheaper then your European conquistadores or any other soldiers. This to enable the Native Americans to support vast armies and keep the European expeditions relatively small in numbers.
The AI might even be tweaked a littleto increase the chance of getting ambushed when in American lands.
There might be a special Victory Condition for the Native Americans like bring the whole of South America under your firm rule and outlive the European factions for so long. Whereas the Europeans will have a more straightforward task such as conquer some 70 regions and destroy or outlive given factions.
This would I think balance both worlds to fit into a campaign without having gaily dressed merrily slaughtred push over faction swhich replaces a more serious threat.
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