I regularly 4-table ring games. I think the hardest for me was adding the 2nd table. Once I got used to dividing my attention between the 2 and making the necessary adjustments (i.e. tightening up a bit), adding the 3rd and 4th was much easier. I have played as many as 6, but that's exceeding my comfort level -- not as enjoyable, too much like work with the constant, hectic back and forth. I'm amazed at people who can 16+ table and not have an anxiety attack...
Having a good HUD is a must because most of us can't possibly watch and keep up with how everyone is playing across multiple tables.
However, I do not like multi-tabling SnG's and tourneys as much, unless I can start them at the same time and they have the same blind structure, speed, etc. If the blind levels get too spread apart between the tables, the constant strategy adjustments required to switch back and forth are just not my cup of tea. I wind up forgetting where I'm at and making the wrong play for the current situation.