No problem installing RSLogix5000 on an external harddrive. There is really no functional difference to an internal one.
The A-B activation file can be on any drive that is accessible(talking about the old A-B activation file here, not the Fatory Talk stuff).
However, trying to run the software from a different computer will give you problems. The reason is the registry is not on that external drive. Basically, the software isn't installed on the other computer. Now if you do identical installs on multiple computers you may be able to make them share the same external drive with software loaded. However, I think you are making it harder than it needs to be. The external drive is generally slower to access, so it has a performance penalty associated with it as well.
If you want to use the software on two computers (one at a time of course) I recommend that you load the software local on both machines. Use the external drive for data (like PLC programs) that can be shared without problems. You can put your activation file on the external drive. (This is for A-B, I have no idea what works for Seimens).
The reason Peter and others are using virtual PCs to load PLC software is that the different manufacturers have a habit of stepping on each other's toes when installing complex software. The virtual PC eliminates this because each instance of a virtual machine has its own operating system and its own registry. Basically, if they won't play well with each other - make then play by themselves.