My friend Lisa will be visiting Gotham with her mother and sister soon, and since I volunteered to make some restaurant recommendations, I thought I would post them here for public consumption/future reference. Comments welcome. I will update this occasionally, and probably make it into something more filter/search-able eventually. As you can see, I have a bias towards restaurants south of 23rd Street, as do all reasonable people.

In somewhat random order, with favorites closer to the top

Lupa [Village]
Moderately-priced, excellent Italian
170 Thompson Street (between Houston and Bleecker)
212-982-5089

Bistrot Margot [NoLiTa/East Soho]
Inexpensive, casual French
26 Prince St (between Mott and Elizabeth)
212-274-1027

Fleur de Sel [Flatiron]
Excellent creative French with moderate prices at lunch, expensive at dinner. The owner, Cyril, is one of my favorite restaurant people in New York, and the restaurant is quite comfortable and unstuffy.
5 East 20th (between Fifth Ave and Broadway)
212-460-9100

The Odeon [Tribeca]
One of our reliable restaurants for years, especially for late-night or mid-afternoon dining. Great fries and chocolate pudding.
145 West Broadway (between Thomas and Duane)
212-233-0507

Wallsé [West Village]
Brilliant nouvelle Austrian restaurant. Expensive, but worth visiting when you can afford it. The best time to go is when they are having an Austrian Wine Dinner on Monday nights. $80 for a five-course/five-wine meal here is an incredible bargain. Dinner only.
344 West 11th Street (at Washinton Street)
212-352-2300

Union Square Cafe
A NYC classic. Expensive, but with an excellent mix of casualness and attentive service with great food.
21 East 16th St. (between Fifth Ave and Union Square)
212-243-4020

Esca [Theatre District]
Southern Italian/Seafood. Brilliant, a bit expensive, but a great wine list and fabulous fish.
402 West 43rd St. (at Ninth Ave)
212-564-7272

Savoy [Soho]
Creative cooking with an emphasis on seasonal ingredients. Excellent, inobstrusive service and a casual environment. You can eat here for a moderate bill or spend a lot of money.
70 Prince St. (between Crosby and Lafayette)
212-219-8570

Raga [East Village]
Indian/French/American fusion. Good food, and moderately priced with a wine list that works with the food.
433 East 6th Street (between Ave A and First Ave)
212-388-0957

Florent [West Village/Meat Packing]
It's open 24 hours again! My backup restaurant in the meat packing district, easily reachable by cab when you can't think of another place, or they're all closed because it's late. Cash only!
69 Gansevoort St.
Between Greenwich and Washington
(Two blocks south of 14th Street)
212-989-5779

Bar Jamon/Casa Mono [Gramercy Park]
Two places: a "ham bar" with great snacks including Spanish ham and wines by the glass, plus a more tapas-y restaurant. Like Lupa and Esca, part of the Batali/Bastianich empire. Moderate prices, great wine lists.
17th Street and Irving Place
212-253-2773

[Update: I added info about Wallsé's wine dinners.]