Originally Posted by mev

It looks like your question is in terms of an extended trip of several months so I'll answer in that context rather than a short one-week or two-week ride.

In terms of longer cross-continent trips, I've done N/S trips:
- Along the Pacific Coast from Vancouver to Tijuana (and then later down Baja)
- Along the Atlantic Coast from Key West to Halifax Nova Scota (and later up through Nova Scotia and out out to St Johns Newfoundland)
- In the middle roughly along US 83 - from Brownsville to the Canadian Border
- From North to South from Prudhoe Bay to Banff to Colorado to Socorro NM and then west to San Diego

I've also done E/W trips:
- Across Canada from Fairbanks to St Johns Newfoundland
- Across Northern US from Astoria Oregon to Portland Maine
- Through the middle from San Jose/Reno/Salt Lake City/Fort Collins/Wichita/Memphis/Cincinnati/Pittsburgh (still need to add Pittsburgh to DC)
- Across Southern US from San Jose to San Diego and southern Tier to St Augustine

You didn't mention time of year but that is also a consideration (Southern Tier not in the summer and some others prefer the summer; a S/N or N/S route also plan the time).

As far as scenery goes between some of these trips: I would put the Pacific Coast at top of the list followed by routes through the Rockies - so either a northern or mid route across the US. I would put the southern tier lower and the east coast is also lower.

As far as people goes, I haven't necessarily found found big differences. There is a trade off between going on an established route e.g. TransAmerica or Pacific Coast - or going off on your own route. It has been in some of these off-route areas where I've connected more but that is at least as much a factor of time I spend. The other factor that sometimes comes into the people is sometimes you can use the bike trip as an excuse to stop in on relatives or family on the way - so that depends on who you know where.