I got to thinking about this after skimming Starks article at the 4-letter network. I guess I'm not that big an advocate for realignment since I pretty much like how things are set up for the Angels. I do get annoyed by inter-league play since I hate watching the pitchers bat (yeah yeah I know there is always Mathis...) But if I was in charge I think this is how I'd set it up. It's basically geographical; some teams could easily be swapped.
Pacific
Western
North
East
South
Playoffs
5 Divisions winners
3 Wildcards based on best record
note: this post has been edited to reflect some good suggestions in the comment section