La Mortella is a gem, a well maintained country villa that has been converted into a boutique hotel. Although you have to drive by a sulfur-smelling warehouse of some sort to get there, the countryside ends up being beautiful, with a pool, gorgeous hills, and friendly, attentive staff. The continental breakfast spread is impressive and La Vivienda restaurant down the hill is excellent for dinner. And the rooms are delightful, with high wood-beamed ceilings and comfortable beds.
As for the area, we would recommend Monte Argentario if you are interested in hiking, sailing, diving or golf (there is a golf resort next door), but not for beach days (not that many beaches) or crawling through old Italian towns -- neither Porto Ercole or Porto Santo Stefano are that inspiring (we didn't get to spend time in Orbetello though).
Since we didn't have a very early flight out of Rome Airport (90 minutes away by car), we chose to stay here instead of an airport hotel, and were delighted we did.