No best, just different...and as the previous poster said, what's your use? If just a nice range and trail companion that can ably defend the camp and bring home just about any game (close in of course), the New Vaquero in the classic .45 is great. If you have the want/need for powerful heavy loads, and especially if you do not reload, the 44 Mag can't be beat, and it can also shoot the milder 44 Special rounds as well. I like 5.5 in that for sight picture, overall balance and felt recoil (muzzle flip) control--but the real world differences are really minimal, and 4-5/8 does carry/pack easier. Yes it is a big heavy gun either way. It also does not have the newer gun's cylinder indexing that aligns (does not overtravel) each charge/eject hole. The New Vaquero (.44 Sp, .45 Colt, .357) does have this nice feature. The two Vaquero variants also have an entirely different grip feel, the newer being smaller and much slimmer--some like, some don't. Doesn't just depend on your hand size but shooting style and just personal preference in grips. Of course , if objectionable, it is fixable with aftermarket grips, as is the large frame Vaquero grips' larger girth if that's a problem in reverse. So, in neither case should that aspect be the deciding factor.
Another choice would be .45 Colt in the larger frame. Vaquero, which can of course take the heavy .45 loads. It is a myth that the New Vaquero can only take "light" or "cowboy" loads. It can take "normal" off-the-shelf .45s, but it is not meant for the super-heavy ("Ruger only") fare reserved for the magnum-class frames (large frame Vaquero, Blackhawk and Super Blackhawk). In these larger guns, .45s can be loaded right up there to meet-or-exceed .44 Mags...but again, if you don't reload, .44 Mag will be easier/more consisent to come by on the shelves.