In your case a slightly used car may hugely advantageous especially if GM/Ford. With your high mileage/year likely highway nearly all vehicles(except for bad luck with one) will have a long engine life as long as maintenance performed.
IMHO your big thing is comfort vs MPG. Small cars do not have the comfort of larger counterparts and also get “old” faster as they cannot absorb the impacts of road as well so they rattle earlier. There is a drastic difference between at 250k between Corolla/Civic/Cobalt vs Camry/Accord/Malibu. Smaller cars turn “old” faster.