Overnight in B'more
I would say stay in Fells Point by the water at Henderson's Wharf, Celie's B&B or the Admiral Fell Inn. There is lots to walk to from there including:
Henningers Tavern www.henningerstavern.com
various Taco Trucks and Tortillerias
the next neighborhood over is Canton, go to Mamas on the Half Shell for Baltimore style seafood: www.mamasonthehalfshell.com
I think Fells Point is a good neighborhood if you want to shop (antiques, knick-knacks) and stroll along cobblestone along the water. There are hotel and restaurant choices a-plenty.
Mt. Vernon would be a better choice if you're interested in doing museums, the symphony, or opera while you are here. The Walters Art Gallery, BSO, and Lyric Operahouse are all in this neighborhood, as are numerous wonderful restaurants. There's also Antique Row on Howard Street. Also some amazing row-homes/architecture and churches to marvel at. Very much a walking neighborhood. Lovely Washington Monument with attendant parks around it.
Abacrombie is a guest house as well as amazing restaurant. There's several other hotels in Mt. Vernon that you can stay at: http://www.mvcd.org/places_to_stay.aspx
Great restaurants in Mt Vernon include Akbar and Mughal Garden (Indian), The Helmand (Afghani), Abacrombie, Brewer's Art (stop in just for a Resurrection Ale), and Dionysus. Never been to Brass Elephant but it gets great reviews. You can walk up the street a bit past Penn Station and go to Tapas Teatro, Zodiac, Sofi's Crepes, and even catch a movie at the Charles. (Or just people-watch the people going to the Charles.) Have a cocktail at Club Charles while you're there. Go to the 13th floor in the Belvedere for a nightcap and see how pretty Baltimore is from above.
If you do stay in Fells Point, also consider Mezze and Kali's Court. Mezze hands-down is my favorite place to eat on a weeknight. I believe the food to be far superior to Pazo.
In terms of vibe, I consider Fells Point to be more a "party" atmosphere, whereas Mt Vernon is more a artsy/eclectic/gay-friendly type of area.
Enjoy Bawlmer, Hon! :)
I agree with many of these recommendations, notably Brewer's Art where the Resurrection is great and the rosemary garlic flies with a side of pure, fatty mayonaise is to die for! If you're looking for something more than casual, try Red Maple. Don't go to Brass Elephant. Too expensive and doesn't meet the hype/expectations.
I'd have to disagree with the Kali's Court/Mezze recommendation. I much prefer Pazo over Kali's any day of the week. Pazo is more fun, inviting, exciting, and the service is top notch. Plus, the food is nearly flawless. Definitely try one of their pizzas and get their empanadas. Simply delicious.