Are 300cc bikes good enough for highway driving nowadays? If not, help me choose a bike!

So let's keep it short. ALL I care about is reliability, longevity, and fuel economy. I'm sticking with Honda for that reason, I know they tend to be extremely reliable.

So, I have it narrowed down to a few bikes.

A new Honda CBR300R
A new Honda CB300R

A low mileage used Honda nc700 or nc750 if I can find one cheap enough.
A low-mileage Honda CB500X

or a low-mileage Honda CB500f

remember I only care about reliability, longevity, and fuel economy. I do not care if the engine size is small and I will not "outgrow" the bike. I'm an experienced rider of street bikes and have owned bigger bikes in the past. I no longer have a need for performance and just want a bike capable of adventure and getting me a really good MPG. This is why I'm going as low as 300cc. If modern 300cc bikes are capable of a lot of highway driving and long-distance I'll totally get a 300c because they would probably have the best mpg. My concern with a 300cc is a lot of highway mileage killing the bike in the long run. I could be totally wrong on that though. I'll also have paniers/luggage on the bike as well, probably nothing super heavy though.


Thoughts?