Pay attention; my advice is coming from someone who understands the 30 largest frequent flyer programs well and has personal experience with about 20 of them. I also fly a TON on a TON of airlines and hold top tier status on all three alliances. Broad experience is needed for sound advice here. It is frustrating to see people recommending their airline when that airline does a very poor job of what the OP said was most important to him.

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THE soni - Welcome to FT! ^ You did post in the right forum and gave almost enough information in your first post; far better than most!

You will want to choose one primary program from one of the three alliances (Oneworld, Skyteam, and Star) and bank everything with that program while flying the entire alliance.

You most important things are:
1) Free upgrades
2) Product quality

There will be a major trade off here.

Lets start with upgrades: It appears you will be flying enough to make top tier on the airline you settle on. You will want to choose a US based program because no international program top tier status will provide you with unlimited domestic and the ability to upgrade almost every international flight for free.

Top tier requires either 75,000 miles flown or 100,000 miles flown in a calendar year to qualify depending on the airline (US airlines considered here). All six US legacy carriers would essentially provide you with unlimited free upgrades on any fare when flying domestically.
What are your chances of clearing domestically as a top tier. Something like:
AA 90% US 90% NW 90% UA 70% DL 70% CO 60%
Aircraft type and route make a ton of difference but overall a domestic F class quality rating from best to worse would look something like:
CO AA UA DL NW US
(UA and AA have the best business class products JFK-LAX/SFO)
Internationally, only two of the legacy carrier give their top tier flyer free systemwide upgrades.
AA gives 8 per year
UA gives 6 per year
These are valid anywhere these airline fly (not on partners!) on most fares including cheap ones.
(DL and US give a few certs that are very hard to use. NW gives 2 certs to those who fly 150,000 miles in year.)
Internationally the other way to upgrade is miles.
NW has a good Asia network but only allows miles upgrades from very high fares.
CO allows upgrades from cheaper fares requiring a large co-pay (ie $450 each way plus lots of miles) and from very expensive fares without the co-pay.
DL doesn't have enough of an Asia network to be a good option.
US doesn't have enough of an Asia network to be a good option.
AA allows upgrades from most cheap fares with miles but requires a co-pay (ie $300 each way).
UA allows upgrades from medium fares and above with miles and does not require a co-pay.

Now for #2, product:
The best business class products transpacific are on Asian carriers including Cathay Pacific, Singapore Airlines, Japan Airlines, All Nippon, and others.
The best business class product transatlantic is arguably on British Airways with other European carriers such as SASE coming in next.
Each of these products can only be upgraded to from cheap fares with miles from that airline's own program. All these programs would award you 50% or less overall of what you would be earning from flying US carriers on discounted coach fares and many of the above either heavily restrict what fares can be upgraded or/and charge 150% to 200% of what their US counterparts do for upgrades. Essentially, you would earn enough upgrade certs and miles to upgrade every flight you take with the best of the US programs but would be looking at being able to upgrade 1/3 of the time at best using most of the above programs trying to upgrade cheap coach to business.

I suggest choosing carriers with decent but inferior business class products so that you can try and upgrade 100% of the time instead of maybe 35%.

The only carriers that will give you sufficient upgrade instruments to try and upgrade 100% of the time are AA and UA. Between the 8 VIP certs AA would give you and AA miles you could upgrade most flights, paying a $300 co-pay to upgrade with miles after you run out of VIPs. International clearance rate for EXPs is something like 90% off peak and 60% peak. UA has a similar international clearance rate for 1Ks. Between the 6 SWU certs UA would give you and UA miles you could upgrade most flights for free...using SWU certs for the cheapies and miles for medium fares.

For AA, with the exceptions of India and China, you would fly JFK-NRT upgrading on AA metal then connect using JAL or CX NRT-anywhere Asia in coach.

For UA you could connect to more places on UA metal (upgrading all the way through) but would usually have to through a USA United hub first.

Both AA and UA give you a 100% mileage bonus when flying them as top tiers. AA also gives this bonus when flying most Oneworld carriers and crediting to AA; UA gives no status bonus crediting Star flights to them. For example, if you fly CX (Cathay Pacific) JFK-HKG AA will give you your status bonus. If you fly NH (All Nippon) to NRT, UA will not give you a status bonus.

AA gives a couple more upgrades; AA allows more really cheap fares to be upgraded with miles than UA. AA charges a co-pay though; UA requires purchase of medium fares but doesn't have the co-pay. UA more Asia destinations themselves; AA more South American destinations themselves.

If free coach to business class upgrades are a priority then you really need to choose between AA and UA.