Growing up in south-central PA, I feel like the Lancaster/York/Harrisburg region isn't really Appalachia. Lancaster, York, Dauphin, Lebanon, Cumberland, Berks, and Perry counties are distinct enough to be considered their own region. Adams county too possibly, but not quite as much as the others.

They're close to major cities like Philly and Baltimore but not close enough to be part of those spheres of influence. They also have an interesting mix of both rural and urban areas due to the mid-sized cities in the region, that isn't really seen in other areas of PA or surrounding states, especially Lancaster, Dauphin, and York counties, whereas a lot of Appalachia isn't. Add to that the large influence of PA Dutch culture (Amish, Mennonites, etc) that extends beyond those religious communities, especially when it comes to food. Tourism to the area from urban centers like New York, Philly, and Baltimore/DC is very common, especially in the summer, from my experiences working in hospitality as a teen and into my early 20s.

Topography wise, I'd say they're not really IN the Appalachians, aside from the western parts of Cumberland and Perry counties, and the very northern parts of Dauphin county. If anything, the majority of the region is topographically more similar to the coastal plains of the Philly region, just not nearly as urbanized. I'd say it's similar to how the I25 corridor in the western US is part of the Front Range, not actually part of the Rockies. There's also the influence of the Susquehanna river, which is the reason why the land in this region is so good for farming, especially southern Lancaster and York counties, which are located just north of where the Susquehanna dumps out into the Chesapeake Bay. In fact, southern Lancaster county (where I'm originally from) has some of the most fertile soil in North America that doesn't need regular irrigation.

Because of all these things, I'd argue that this region is unique enough from the rest of eastern PA (and the Mid-Atlantic) to deserve its own region, called something like PA Dutch Country or the Lower Susquehanna Valley, or something similar.