In mainland Greece, we only drove from Athens to Napflio, and in that area. The highways and other roads were quite fine. In all it seemed on par with other countries we've driven in, particularly Spain. I'd say it was a level less in difficulty comparing that with Crete, although in Crete we drove through more rural areas while in Greece we were on tourist routes for the most part. By navigating with a GPS you're not relying on the road signs so much; the road signs become more like confirmation for where to turn or that you're still on the correct route. All tourist destinations were also signed in English. BTW when we picked up the rental car in Crete we could not figure out how to get the car-based one to work, and neither could the rental agent, so we were glad we had our own on-phone navigation. I've used the Here app for several trips. It allows you to download the entire country map and navigate with no internet access. We did end up returning a rental car in Athens and that was terrible. I chose what I thought was a suburban rental office, and it was still terrible due to crazy late evening traffic. If I were returning a car in Athens area I would return it to the airport.
My husband commented that happily there were no tight squeeze scenarios in our week driving in Crete, e.g. we did not have to retract the side mirrors to get past a narrow spot, or lighten the car (everyone, everything out) to negotiate exiting a parking garage. We did structure the trip so that we didn't drive in either Heraklio or Chania : ) IMO it's best to stay on the main roads in Crete; don't take that short cut that looks oh-so-promising if it puts you on the most minor roads on the map, unless you are not concerned with trip time. As I read somewhere else, a short cut in Crete usually isn't one. On secondary roads you'll sometimes find hairpin curves, blind curves which are not quite two car widths, heights with no guard rails, animals in the road (many), fallen rock in the road, etc. We tried to do as the other drivers did, e.g. a tap on the horn on a narrow blind curve. It sounds like you are an experienced and confident driver, so you should be fine. My husband actually enjoyed the driving there. It is a very beautiful country.