There are so many great places. You could head down to Boston, catch a show, eat great food.
Go to the Manchester/Nashua area of New Hampshire. See the Currier Art Museum. Go to Pickity Place for a unique lunch. Sunday brunch at the Bedford Village Inn...heck, you could stay there. Dine at Lucia's Tavola, XO on Elm, Mint Bistro (if they are open again yet), Michael Timothys.
Stay up in the White Mountains...not too familiar with the dining scene there, but there are some beautiful hotels.
Burlington VT...Shelburne Museum. Winery and cheese trail. Burlington has lots of places to eat.
212 Main St., Nashua, NH 03060
181 Route 13, Brookline, NH 03033
Manchester, NH, Manchester, NH
I live in Nashua, and I have to say that I would NOT recommend Southern NH as a location for a foodie getaway. There are an increasing number of choices in Nashua/Manchester/Concord like Republic, Sunny's Table and BVI, but this is not an area for a vacation. I'd be so disappointed if my significant other told me we were going on a trip to Manchester, NH.
Go to Portland, ME. The food, the sites and environment are all better.
Try Fore Street and Hugo's in Portland.
Is Boston an option? Lots of good choices there, too.
288 Fore Street, Portland, ME 04101
I agree with this whole-heartedly. I would love to spend a full weekend in Portland...went for a day and didn't get to experience nearly enough (though I still dream about the bread from Standard Baking).
I would also suggest Boston, and if you haven't been to the So. NE board, Providence and Southern CT are great choices too (PVD having the better all-around experience).
Midcoast, midcoast, midcoast. It has the best balance of great dining options and stunning natural scenery...with the added bonus that it has the best restaurant in New England - Primo in Rockland. Make your base in the Camden/Rockland area...you'll have at least a dozen good B&B options. And Acadia National Park in Bar Harbor can be an easy day trip. There's my plug.
Although, if you consider Quebec City to be "southern Quebec", that's pretty hard to beat for a long weekend away...I must admit.
MidCoast's suggestion about Bar Harbor reminds me of a trip my hub and I took a few years ago. We always went in summer when it was the most crowded, but that time we went in winter and stayed at a little B&B where we were the only guests. My best memory is walking together arm in arm down main street in the evening after dinner. All the street lights were on and big flakes of snow were coming down. It's hard to believe, but we were the only people on the street. There were no cars and no pedestrians. Just us. Anyway, I think a trip there in May would be good before the hordes arrive.
Living here, I have to second Portland! It's got everything a foodie could ask for from great breakfasts to some of the best chefs anywhere, all within walking distance of each other. Plus there are a lot of things to do between meals. Google the Bon Appetit article on Portland for a nice overview on why they named it "the Foodiest Small Town in America". There are other great restaurants in New England but not in the concentration that we have in Portland.