I'm a big fan of the S6 and have several, but I've been fortunate enough to get them all at retail pricing, some when they were released online, and others at Knob Creek when they made a surprise appearance last Fall. If you go through the secondary market, they'll cost more. If you can, go to Blade or Knob Creek or Blade West or the Indy 1500 shows. Chances are that they won't have S6s (although they might), but they'll have other stuff and it makes a big difference to be able to pick up a knife and see what it feels like in your hand before you decide what to buy.

Now what you asked for:
I don't have my (De)Regulators yet (hopefully today, I'm feeling impatient), so this is based on the reports of others, but Regulators have a thicker blade, so are heavier overall and more blade-heavy than S6s. For me, I doubt that the handle will feel better (in my hand) than an S6 does, but that's simply because an S6 feels so close to perfect. That's the bad stuff, and it's fairly minor.

On the good side, Regulators are available right now in the store, and at a special offering price -- availability is a very big deal when you're looking for these knives. They're both very strong knives that you can feel confident betting your life on, and SR-101 has a reputation for holding an edge better than SR-77. That doesn't mean that SR-77 won't hold an edge better than most steels on the market after Dan heat treats it, but many claim that SR-101 is even better. The Regulator/Deregulator special offering price includes a great deal on a sheath. If you come across an S6 at retail pricing sometime, then I'd say grab it, but if you don't get a Regulator while the Military Overruns are still available, you'll probably regret it.