I went thru this type of exercise about 4 years ago when I was told I would start to travel a ton... I think you have to download and read the various program details. You have to do a lot of work to make anything approaching an informed decision. And it sucks if you get one year in and you realize you didnt make the right choice. If you are going to fly 100-150k, you have lots of good options and you should study carefully.

I can tell you that I looked at all the majors in the US and my feeling was that I wanted something that could take me both east bound and west bound from my (then) base of Seattle. I also wanted to insure upgrades, although I wasnt really looking for free, I just wanted a good chance with miles. As others have pointed out, upgrades (realistic and cost effective ones at least) are best if you can fly on your elite carrier (or a partner who actually extends upgrade priviliges) the entire flight. For me NW did the job well. Although I've often bought Biz tix, I also needed to upgrade (me and/or my wife) from economy and I found that their scheme for upgrades (including the KLM network) on Y and B fares actually works out pretty well. It's not cheap, but then again paying for Biz isnt either. You probably wont be rolling in the miles for a year or so such that you think using miles to upgrade is anything close to free, but once you are, 30k or 60k for a roundtrip will seem close to free. I think UA was almost equal in my calculations, but I took NW because they were upgrading their fleets to a angle-flat seat which I prefer over the UA recliners. I never seriously considered AA, DL or CO because they just didnt go enough of the places I planned to fly. As for the euro and asia carriers, I didnt want to lose out on the miles from the cheap-o intra-US flights that I took (in discounted Economy as per our travel policy).

From a cost and a certainty standpoint I'm pretty happy with the years I've spent with NW- I've never, ever, ever, sat in the back on an international flight, and only have a few exceptions on domestic flights. There was a lot of planning and shuffling, but most of the folks on this board will do that, I think there are few here that just tell their corp travel agent "get me from A to B on this date." If you are thinking you are going to get the cheapest coach ticket and always get an upgrade with miles (or even more unlikely a "free" upgrade) on international flights and you find that, then let me know the program you find, I'll be right behind you. I also think NW has bumped up a notch this year, for high mileage fliers we'll be getting 4 SWU's when we cross 160k (2 at 120k and 2 more at 160k).

One final thing to consider if you are going to be a serious high mileage guy and you have some flexibility in how your tickets get purchased (i.e. you are not a slave to a US based corporate travel agent). There are some much better fares for various alliances that depart from some obscure places around the world. So if you can get yourself out there on a one way ticket and you dont need to account for both/all legs of a trip on one expense report, then you might find some creative ways so that you can fly in business class and only pay coach fares, this is the ultimate "free" upgrade. When I hear people telling me they paid $7kUS for a simple roundtrip US-asia, I laugh knowing that I'll get at least 4 trips in paid C back home to the US this year for the price of that single ticket.