Almost everything.
Pythons were hand built semi custom revolvers. Best action ever devised on a revolver. Cobra's look the same but are totally different guns with different mechanicals. Cobra's were built on an assembly line and machine fitted. Cobras have the modern transfer bar. KC is one of the strongest most durable guns you can find. Pythons when you can find them without forking over one of your kids or your house were strong but need a bit more care.
Pythons had a special bluing that Colt didn't use on any other gun.
This is a great description I borrowed from dfariswheel on the Colt Forum. He really knows his stuff
The Python action was originally designed in the 1890's and was finalized in the Colt Army Special of 1908.
The Army Special frame and action was used on all Colt medium frame revolvers up until the last Pythons were made in 2004.
The frame was identified after WWII by letter codes. The models fitted with the firing pin on the hammer were the Colt "E" frame, the Colt 3-5-7 Model and the Python both had the firing pin inside the frame and were the Colt "I" frame.
These guns all used the same frame and action design, so they are usually just known as the Colt "E&I" frame models.
The action uses a "Vee" spring to power the entire action, and has two internal safety devices.
One is the rebounding hammer, the second is a hammer block.
When the trigger is released, it's forced back, "rebounded" and locked so it can't move forward.
As an extra level of safety the Colt Positive Lock is a bar of steel that is moved downward when the trigger is pulled, clearing the path of the hammer to fire the gun.
These actions are very complex, with each part performing at least two totally different functions. This is why the old Colt action is often known as a "watchmakers gun" and why so few people are qualified to work on them today.
These actions are know for the smoothness and quality of the single action trigger pull, and the very smooth double action pull that "stacks" or gets heavier as the trigger is pulled.
These models were totally hand fitted at the factory using forged steel parts. A Master fitter assembled the action by stoning and even bending parts to get a working gun.
The Python received even more fitting and smoothing of the action by Colt's top Master fitters.
The Python received Colt's famous Royal Blue finish, later bright nickel, electroless nickel known as Royal Coltguard, and stainless steel in both satin and bright polish.
The Python was the finest finished double action revolver made in America and was more or less a semi-custom revolver, intended to be the best quality revolver made.
In 1969 Colt was pricing itself out of the revolver market due to the large amount of hand fitting needed just to assemble an old style revolver action.
So, in 1969 Colt introduced a totally new type or revolver using "machine fitted" parts.
Instead of stoning and bending parts, a lesser trained fitter assembled the gun by pulling parts from a bin and test fitting until a part fit.
These parts were not made of forged steel, but were cast using a form of powdered metal casting similar to todays MIM (Metal Injection Molding) process.
The parts are made to such tight tolerances, it's possible to assemble a gun by test fitting parts from a bin.
The Mark III was the worlds first "machine fitted" revolver.
The new gun known as the Mark III had a totally different action using a transfer bar safety-ignition system.
When the trigger is pulled, a steel bar rises up between the hammer and the firing pin and when the hammer drops the force is transfered by the bar to the firing pin.
When the trigger is released the bar is pulled down from between the hammer and firing pin and the hammer cannot physically touch the firing pin. This system worked so well, virtually every double action and many single action revolvers have basically copied Colt's design.
The new design used coil springs instead of the old "vee" spring action and the feel of the actions are quite different. These later guns don't have the smooth feel of the older guns, and the actual operation feels totally different.
The Mark III was a success and Colt used the basic design from then on in the Trooper Mark V, the King Cobra, the Anaconda, and in the stainless steel small framed models like the Magnum Carry.
These later Colt's are no where near the hand built quality of the Python and are not as well fitted or finished as the super premium Python.
If you were comparing cars to Colt's the Python was a Corvette, the Mark V was a very nice model Chevy.
Due in large part to the design of the action and how the cylinder is aligned with the bore, and the tapered bore, very high quality barrel, the Python is famous as America's most accurate double action revolver.
While the Mark V also has a high quality Colt barrel, the different action causes the Mark V to be less accurate then the Python.
So, the Trooper Mark V was intended to be Colt's best quality holster revolver for police and most civilian use, the Python was a super-premium absolute top of the line hand fitted semi-custom revolver.