Pic: A salt marsh in Wellfleet, MA
A Canadian reader asked for a post on this topic. A complicated topic, because it depends on the season and on your interests. It's a varied place for such a compact area, with rivers, lakes, mountains, coasts, islands, rural lands, some charming antique towns, lots of decrepit small towns with tattoos, meth labs, and empty old mills; a handful of booming suburban towns of little interest, plenty of music, theater, and dance festivals, and a small handful of pleasant cities.
When driving around, one must bear in mind that most industry, and farming, fled New England in the past 60-100 years for more business-friendly and farm-friendly locations, so it is no longer the prosperous heart of America. Now it's mostly "Blue states", if you know what I mean.
For road food, I'd recommend diners, diner-like one-off places, and seafood shacks instead of fast food chains. There is even an excellent southern barbecue joint on Rte 91, as rickety as heck and the real deal (only during summertime - owner lives in Mississippi). With all the immigrants, there is good Thai food almost everywhere, but the Chinese food in New England tends to be terrible as does Italian food outside of cities except for pizza.
Rather than describing the places I know and enjoy, I'll list just a few and refer you to some good resources. For local flavor, I like Grand Manan Island (between Maine and Canada), Monhegan Island, Camden, Maine, Kennebunkport is touristy but Acadia Park, Cape Cod (Chatham, Wellfleet - lots of Quebec and Ontario license plates there in August), Block Island, The Massachusetts Berkshires - Lenox, Stockbridge, etc - Boston (haven't been there for years though), touristy Woodstock, VT, Stowe, VT, Lake Winnipesaukee and Squam Lake (New Hampshire), Watch Hill and Newport (Rhode Island) - well, it's too much to list and I'll leave too much out so I'll quit there.
We like Karen Brown at lot (her guides for places all around the world are our favorites), and she avoids fancy modern hotels that can make you feel like you are anywhere.
Backroads of New England: Your Guide to Scenic Getaways & Adventures
Lonely Planet New England's Best Trips- 32 amazing road trips
Maybe readers can offer some of their favorite charming New England spots - with interesting things to see, do, and eat - in the comments.