I isolated the hell out of the characters in my modern CoC game a few times...
(1) An huge, Elder Thing complex a mile under the Sonora Desert. (One way in/out, and cell phones sure as hell don't work)
(2) Aulavik Park on Northern Banks Island.
(3) A temporal shift to a hidden shrine, only accessible under the light of Polaris.
Finally, they work for the "big guns" against supernatural threats. If I take out their bosses, or make them distrust their bosses, it's an effective degree of isolation even though they're in the middle of a city.
-O