The various airlines FF programs are constantly changing right now, but you should examine what you want the most out of the FF program. Some considerations:

1)Schedule. If one airline consistantly has the best times/routes from your city, and you care about the shortest routing for your flights (ie save time, connections, headaches), maybe that should be the airline of your choice, and then live with whatever pros/cons that airlines FF program has. The partners of the "best" airline in this case will also help out as you can earn miles on partner airlines.

2)Flexibility of changing awards. AA & NW now charge $100 for ANY change to a FF award ticket (unless you are Plat I think), including dates/times to the same destination. United doesn't charge for those changes as long as the routing is exactly the same (including connection city). Delta doesn't charge for those changes as long as the departure/destination are the same. However, Delta doesn't allow standbys anymore, though they will put you on any available seat the day of your travel for $25 if the FF seat is not available. I believe (not sure) other airlines allow standby flights.

3) Flexibility of getting awards. A million FF miles are no good if you can't get seats. Other than using ~2x the award miles and going "rulebuster/aanytime/etc", are seats fairly easy to get using the min award mileage domestically and/or internationally (as your choice of travel)? The partners a plan has greatly enhances the seat availability. NW/CO and now Delta have a domestic alliance. Alaska/AA (and others?) have a domestic alliance. United/Delta just broke their domestic alliance. Check each airline for international alliances (NW/KLM, AA/Quantas, etc). Partners can also earn miles on each other's FF programs, so you can choose to earn NW miles if you fly a CO flight, for example.

4)Upgrades/Top Tier. If you truly fly very often, then upgrades and additional top tier comfort amenities may be important to you. Check how easy it is to achieve top tier status(Silver/Gold/Plat) and what that gets you. I personally have found it impossible to use my AA earned upgrades (they used to have 500mile upgrade coupons) when I was earned Gold AA. Not only were the upgrades not available on all the legs of my flight (which made the flight not-upgradable), but also I had to round up 500miles for each segment (ie if the flight was 1001 miles, I had to use 3x500mile upgrade coupons). I think AA changed this policy now, but I'm not sure (I switched out of AA FF program). On the other hand, NW is extremely generous on upgrades. If you are a tier member, they automatically upgrade you if there is space available; the higher the tier, the earlier the upgrade confirmation. NW tier seemed to be very helpful in other situations as well, personal experience w/ my dad. He was Silver or Gold NW and had some medical incidences w/ my mom when they were vacationing. NW got them immediate award seats on otherwise "sold-out" flights with waived penalties. That was several years ago, I don't know if their waived penalities policy is the same now. Gold AA seemed a dime-a-dozen, I don't know if everyone earned them or somehow got comped the status. Very little added value except bonus miles and "early boarding" along w/ like 50 other "early boarders".

AA used to be my FF program of choice: best scheduling, fairly easy FF award flights, no penalty for changes, bad upgrades though --- but their program changed. The things that caused me to leave AA were $100 penalty for ANY change to a FF ticket, award seats seemed harder to get, and convenient flight schedules scaled back (and CSR/flt staff seemed to get nastier -- but maybe that was just my own bad experience). I am somewhat in FF limbo right now, I have amassed miles in Delta and NW. But I am not flying much now (except for award travel), so I am not watching it as closely. I know a lot of people are leaving Delta because of their poor top tier earning/benefits (I think), but I personally have recently found their 25k domestic award availability VERY generous -- during Thanksgiving and Christmas.