Everything depends on the workflows being used (or actually their agent determination logic). If the agent determination is based on the organizational structure, then most likely nothing special is required: just forward the existing work items to a new user, and the new workflows should know to whom the new work items should be delivered (=Rick's and Paul's point of view).
But what if in some workflow(s) your agents are determined for example based on some Z-table (the user ID has been maintained there)? Of course you will need some kind of solution for this. Someone needs to go to maintain the new user/employee there. This was just an example, but you should get the idea: everything depends on the workflow and its agent determination. Permanent substitution basically covers everything, but I would not recommend it either.
One idea is to implement one of the BAdIs in the HR area. Basically you can have your custom code whenever an employee gets "terminated". You can do some things automatically there, or send email to someone or whatever.
Regards,
Karri