To be fair, these "large cities" you speak of today were nothing in the early to mid 1800's when the borders were drawn. The only city that really mattered to anyone was New Orleans, and at the time, the French had complete control it for about 10-15 years AFTER Mississippi became a state. New Orleans never had a snowman's chance in hell of winding up in Mississippi. Mobile, maybe... but we had our own coast that has/had opportunity.
Hattiesburg, Tupelo, Columbus, and Starkville just did not have the opportunity to grow because their locations were not near as pristine as Meridian's.
As I stated earlier, at the end of the 19th Century, Meridian was one of the largest and richest cities in the state (it was actually one of the largest cities in the southeast). It was a thriving railroad community. As the highway network grew, it became a major intersection for Interstates 20 and 59. Natchez was a resort town for the rich plantation owners, and Jackson was nothing more than a small town up on a bluff. Hell, even Greenwood was a large, industrious, and fairly wealthy city. Meridian, Jackson, Hattiesburg, and even the coast had every chance in the world to become iconic southern cities like Atlanta or Memphis, but like I said, some powerful locals fought tooth and nail to make sure that Meridian and cities throughout the state never had a chance to grow and prosper.
ETA: I had my dates screwed up... the Louisiana Purchase was in 1803... Mississippi became a state in 1817. My bad... either way, it was part of the Louisiana purchase and the Mississippi Territory was not going to end up with New Orleans.