However, if you eliminate the Mississippi, you also have to eliminate/completely alter the courses of the Missouri, Arkansas, Red, Ohio, Tennessee, and numerous other feeder rivers.
But if the river that flows roughly in the same pattern as OTL Ohio, but then flows into the ATL St Lawrence that takes everything back towards the Northeast, then a huge swath of North America (Mississippi River basin) will be much more isolated from the Northeast. I suppose you could create a St Lawrence river basin that includes much of OTL Mississippi basin, but I can't see how rivers in the Southern part of OTL US would be a part of the basin. All in all I think you end up with a continent that has more areas of isolation than OTL continent has.