I've tried Bose QC15 noise cancelling; Bose QC3 noise cancelling, Sennheiser PXC 300 noise cancelling, Dr Dre Monster Studio Beats noise cancelling, Audio Technica ATH-CKS90NC noise cancelling , Sony in-ear MDR NC22 noise cancelling and a JVC on-ear (cannot recall the model but noise cancelling or noise isolating) headphones/earphones. All help a lot, and are very much better than standard issue hard on-ear airline issue headphones, although the difference is less when compared with the cushion style headphones issued in some Business Classes.
All have their pluses and minuses. Some are very bulky (eg Bose QC3 surround ear headphones and Dre Dre Monster Beats); some will not work if the battery is flat (again Bose3 headphones; those that fit in-ear need to be just the right size for ones ear or they let in too much sound/fall out easily or put uncomfortable pressure on the ear canals.
However, it is in large part a matter of taste - in-ear styles are more comfortable than on-ear or surround-ear headphones when sleeping on one's side, but I find them annoying on very long flights. I found a small but very welcome difference in noise cancellation, comfort and bulk between the Bose QC3 headphones and the Bose QC15 headphones. I personally prefer disposable batteries (as in the QC15 headphiones) to the proprietary rechargeable ones in the Bose QC3 headphones.
Of them all, I recommend the Bose QC15 headphones for long flights, but I also take my Sony in-ear earphones with me as they take up almost no space and can be used when my BOse QC15 have issues like flat batteries. But you should read reviews and ask fellow travellors.