Also see my reply in the general Handguns section.
Colt is still very much in business. Parts are not an issue with Pythons, though local gunsmiths that are capable of working on Colt D, E, and I frame revolvers may be. There are a couple of nationally known firms that do good quality work on these Colt arms, and more than a few 'smiths that do work as good or better.
The cylinder length issue for cartridges loaded with long nosed lead bullets applies also to some S&W's, as well as to some other makes and models. I might note that the original ammunition made by Winchester for the .357 Mag had bullets more like Phil Sharpe's design than Elmer Kieth's for this reason.
Colt D,E, & I frame revolvers will not, in general, withstand rough handling that many other makes will accept. This is largely due to the unique positive cylinder lock up attained through design just before firing. No other current production revolver can be timed as closely; the price paid is that maintenance is necessary more often than with other designs. If you shoot mostly 38 Specials, this really isn't much of a concern, if you shoot mostly 357's you'll probably have to service a Python at about 10,000 round intervals.
One reason to purchase a Colt D, E, and I frame revolver: you like the trigger. One reason not to purchase a Colt D, E, or I frame revolver: you don't like the trigger. If you know anyone that owns one of these Colt revolvers, ask to go shooting with him/her so that you can see what you think.
Bob