It is more about what you are comfortable with, especially if something breaks and you have to react on the fly. When we were in London there was a tube strike and we had to scramble a bit, luckily a Bobby was able to help us out. Boston is wicked safe so don't really worry about that.

If you don't want to stay right downtown, look at Somerville, Quincy, Cambridge, Malden, Revere. Many of the hotels do a pick up/drop off situation from the local transit stop.

Avoid coming over the 3rd week of April, everything is expensive and full.