The big difference is, the King Cobra was designed to be "machine fitted".
That is, the parts were made to very close tolerances and the revolver was assembled by pulling parts from a bin until a fit was achieved.
The Python is a product of two centuries ago.
The direct ancestor of the Python was designed in the late 1890's and perfected in 1908.
The Python is manufactured by making parts over-sized.
A Master fitter assembles the parts by carefully stoning and filing until a perfect fit is achieved.
This requires a LOT of time by the most highly paid workers Colt has, and this level of hand labor and finishing accounts for the Python's high price.
The King Cobra is the last version of a revolver first introduced in 1969 with the Trooper Mark III.
These revolvers have nothing in common with the Python, being totally different designs.
While the King Cobra has a modern transfer bar ignition, (Colt developed the first modern transfer bar system, which virtually every revolver maker in the world has copied) the Python has the older type revolver system of hammer block safeties.
The Python has the only "bank vault" lock-up ever used in which the cylinder is tightly locked in PERFECT alignment with the bore at the instant of ignition.
This insures the bullet enters the bore with no deformation, and along with the Python's tapered bore accounts for the Python's reputation for the best consistent accuracy of any double action revolver.
The down side is the cost of the revolver, and that the action MUST be in absolutely perfect adjustment to work at all.
The King Cobra uses the modern system used by all revolvers in which the cylinder is NOT tightly locked at ignition.
This allows the cylinder to align itself with the bore.
While this costs less money to build, the bullet doesn't enter the bore perfectly, and is distorted, degrading accuracy slightly.
The action is cheaper to make, but accuracy isn't what it could be.
The basic difference is, the King Cobra is a modern, super-strong revolver made for the mass market.
Master gunsmith Jerry Kuhnhausen believed the trooper Mark III/King Cobra was very possibly the strongest mid-frame revolver ever built, due to Colt's high-grade forged and heat treated frames and cylinders.
The Python is a relic of another age, like a Rolls Royce. It's essentially a true custom-built, hand fitted and hand finished revolver.
The Python is like a Lamborgini sports car. It's expensive, and you have to treat it like the expensive speciality item it is.
You can't treat it like a cheap pickup truck, and batter it to death by mistreating it.
If you want a good shooter revolver that's at least 1/2 a step above other brands of revolvers, and want a real tank of a hand gun, the King Cobra is it.
If you want, and can afford the finest hand made production revolver in the world, the Python fills the bill.