The "Boston in a Day" tour that I usually take friends on starts by following the Freedom Trail from Park Street Station, with lunch at Fanueil Hall, and then dessert in the North End. Then we head back over towards Park Street, through the Public Gardens, down Newbury Street (if shopping isn't your thing, and it's all upscale chain stores so that's understandable, go down Commonwealth Avenue and enjoy the peace... fun fact: zoning rules at the time said those houses could only be 3 stories tall. Good thing Mansard Rooves were in style at the time!) to Dartmouth Street, then up to Copley Square to admire the famous church/Hancock Tower dichotomy. Then across the street to Boston's absolute best kept architectural secret, the Boston Public Library. LOVE this building, and I bore everyone I know to tears by telling them all about it
Make sure to go up to the 3rd floor and look at the Sargeant murals: he considered them his absolute masterpiece and legacy, but they've kind of been roundly and consistantly panned since he did them! Still worth a look if you like art. From there the South End is only a few blocks over, and that sounds like it would be right up your line.
Yes this route is very touristy, but you also get to see a good portion of the city, and there are lots of little places along the way to stop in and hang out or shop.
I should note that I used to be a tour guide, so I actually bore my friends all throughout the day telling them more than they ever wanted to know about everything! And the nice thing about Boston is that it's nice and compact, and definitely a "walking city," so you can see much of what you want to see in a day... and obviously if you have longer than that there's no need to rush.
When you get up here, take a look at a free magazine you'll find on many corners called The Improper Bostonian. They have listings of all the exhibits, shows, events, etc that are happening at the time. We have lots of smaller museums that most people haven't heard of but which sometimes have really amazing little shows.