Ron a Prerequisite only once
Hope pre-requisite you are going to add is an another setup.exe,which had been created via installshield.In that case you can write Installscript function which will set registry key on successful installation using functions like RegDBSetDefaultRoot,RegDBCreateKeyEx,RegDBSetKey as mentioned in example given in the below link:
You can create InstallScript custom-action which can call the specific function that can be sequenced on successful installation.Now registry key has been created.
You can process with registry based condition using Pre-requisite editor,rest all you might know i guess.
Since pre-requisite editor is just an editor ,it can't create registry entries.
Hope it helps,