Having flown frequently from BOS-SFO I've often faced the same question, although I think all BOS-SFO flights are 767's now.

Business Class has a more comfortable seat assuming you're not in one of the 767-200 domestics. If your flight involves a red-eye flight, avoid the 757 like the plague.

Two Class First seems to have a slightly superior food service, although I think it would only be noticable to someone whose flown it several times. The only differences I can spot are that two class first has more personalized service with less options, but business has a few extra options with less personallized options.
For example, the business class desert has 3 choices, one of which being a scoop of ice cream. But on the 757, dessert has sundaes or cheese.

Of course, you'll need to take the Admiral's club into account too. 1st class trans-con's may enter (2 or 3 class), but not business.