A large-scale eruption of Popocatepetl would definitely affect Mexico City and Peubla, since on clear days you can clearly the top of that volcano from both cities. The effect on Mexico’s economy would be huge, since Mexico City is the country’s capital and Puebla is a major industrial center (with the largest Volkswagen factory outside of Germany).
The impact would send a massive human wave north towards us if it happened.
I would imagine even the cities of Toluca and Pachuca would also be impacted heavily.