Surely any a/c entering airspace where there is commercial traffic under IFR performing IFR approaches should announce itself to ATC, even if VFR, and have mode S ON.
In the US, virtually every airliner route under IFR flies through Class E airspace where VFR traffic is not required to be in ATC contact and is unlikely to have Mode S. The key is understanding that IFR in Class E does not provide a 'sterile' environment in visual conditions, and flying accordingly. Eagleflyer's post lays that out pretty well, for all concerned.