As with the Realms, the easiest solution is to place Ptolus somewhere remote; perhaps off the continent of Khorvaire entirely. Xen'drik has lots of empty space into which to plop a city.
One interesting idea might be to slap the city and its environs in the middle of the Mournland; maybe Ptolus is an island of safety in the midst of that blasted land (or perhaps it's drawing its power from the Mournland itself!).
One idea I like (though it does require some historic retooling) would be to make Ptolus the ancient capital of Galifar. Putting it in the center of the Mournland would probably work well with this; perhas the assaults on the city created so much collateral damage as to render the surrounding land a waste, but Ptolus and its environs survived through powerful magic.
If the Sharn sourcebook weren't so excellent, I'd consider replacing Sharn with Ptolus, but the former city seems a bit too iconic to Eberron to dispense with.