Riding styles or techniques and in particular whether you like to shift or not makes the biggest differences in whether one is satisfied with a half liter bike that gets 60 mpg or one
must have a bigger liter bike or more
to ride safely.
My 40 HP GS500 for example is a six speed and moves along quite nicely on interstates at 75 mph indicated in 6th gear. If more zip is needed for a steeper hill or to pass, dropping down to 5th or even 4th is automatic with experience and is even necessary to pass safely on 2 lane roads.
When I used to run with big twin friends more often than I do now, I'd generally just leave it in 5th gear on freeways to match their roll on speeds and even dropping to 4th is quick and easy for more pull. The GS redlines in 4th at over 100 mph so it's no problem to do so.
For running at a good pace with bigger bore bikes in the mountain twisties, I'd keep the tach needle between 7k and 9k rpm. Shifting up at 9k just above the HP peak and downshifting around 7k at the torque peak to keep the revs up. Can maintain a very good pace running like that on a small cc bike and it's much fun doing so. If I come home without doing at least a thousand shifts, I feel like I've been out there loafing along.
Sure wish they'd put tachs on cruisers too like they did in the 80's, might have to get one some day to still be able to get on. If you really don't like to shift, get the big cc bike.

407,211 miles in 30.1 years for 13,528 miles/year average. Started 7/21/84, updated 8/26/14