What is the difference between mining with multiple workers vs single? Some bitcoin mining clients mine on a single worker, while other clients allow multiple workers.  How will either of these options affect mining production?
Depends. Generally you'd use multiple workers when you have multiple machines (ie graphics cards, mining rigs, or a farm of USB sticks). In some cases you could have them all combined and contributing to a single worker but usually this is not desirable because you'd want to keep track of how each device is performing.  

If for no other reason, that certainly makes it easier to tell which one has crashed or is not working when problems arise. 

Some hardware&amp;software combinations might produce slightly more from running on two workers at once but in most cases I think that's unlikely.