MLB has not expanded since 1998, while the NFL, NBA and NHL have all expanded since then. No new teams will be added before at least 2015, making this the longest MLB has gone without expanding - other than the 60 years from 1901 until 1961.
I propose adding new franchises in Charlotte and Memphis, having Arizona and Tampa Bay switch leagues, and then realigning into eight 4-team divisions, similar to the NFL.
East - New York, Philadelphia, Pittsburgh and Washington.
South - Atlanta, Charlotte, Miami and Tampa Bay.
North - Chicago, Cincinnati, Milwaukee and Saint Louis.
West - Colorado, Los Angeles, San Diego and San Francisco.
East - Baltimore, Boston, New York and Toronto.
North - Chicago, Cleveland, Detroit and Minnesota.
South - Arizona, Houston, Memphis and Texas.
West - Kansas City, Los Angeles, Oakland and Seattle.
The Cardinals would play two 4-game home and two 4-game road series' versus the Cubs, Reds and Brewers = 48 games, one 3-game home and one 3-game road series versus the other 12 National League teams = 72 games, one 3-game home and one 3-game road series versus the 4 teams in one of the American League divisions ( alternated each season ) = 24 games, and finally one 3-game home and one 3-game road series versus the Royals = 6 games. This adds up to a 150 game regular season.
Each team would have one natural rival from the other league - SL/KC, CHI/CHI, NY/NY, LA/LA, SF/OAK, WAS/BAL, CIN/CLE, MIL/MIN, COL/SEA, SD/ARI, PHI/BOS, PIT/DET, ATL/HOU, MIA/TEX, TB/TOR and CHA/MEM.
Either 10 or 12 teams would qualify for the playoffs, with the top 2 or 3 division winners in each league receiving 1st round byes. The 1st round would be best 2 of 3, with all 3 games played at the home of the division winners. The league divisional series', league championship series' and World Series would all be best 5 of 9, with a 3-4-2 format.