Depending on how close you want to stay to the Park, the Hotel Commonwealth is a great option right in Kenmore Square (steps from Fenway), and on the Green Line subway stop.
For a "large" US city, Boston doesn't feel all that big within city limits, it's closed in and easily walkable, with great restaurants all over, so tough to really go wrong in any area. Probably, as others have said, the best area to utilize the whole city easily is the Prudential area of the Back Bay which is centralized relative to the waterfront and Fenway Park. But in my opinion, if you want to stay right in the Fenway area, tough to go wrong with the Hotel Commonwealth.
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