The issue with that is demographics change over time, so any attempt to break states up into more politically/economically uniform pieces will become outdated o

The issue with that is demographics change over time, so any attempt to break states up into more politically/economically uniform pieces will become outdated over time (like if a large city expands beyond its current boundaries). So you'll have to change the state lines periodically, and then you've still got the issues of redistricting, only now on a national level instead of a state level.