The only definitive clue we have as to Megaurbanopolis' location are the call letters to the TV station, KBTTF (BTTF= Back to the Future, naturally), from the Manicoid episode. Stations with Ws as the first letter are east of the Mississippi River, while stations that start with K- are west of said river. A typical gimmick used in adventure shows and movies is to display a map, and then have a red line trace the path of a journey from destination to destination. Since the location of Megaurbanopolis, or Metro, is NOT specifically mentioned, this is probably why no map-tracing was done (well, besides the added production cost) when Wendy flew to the rescue of Em-Em and Sensei Ping in the Middlejet, or when Em-Em, Dubby, and Guy Goddard sailed to the Candle's Island in the Cancer Sub, ahem, the Middlesub.

I believe that in the Sino-Mexican Revolution, a stock establishing shot of the Los Angeles skyline was used. However, I think that this can be dealt with in future episodes by inserting skyline shots of other cities in order to completely befuddle the Middlefans.