We really enjoyed our stay at mainhaus Stadthotel Frankfurt. The hotel is on the east side of old-town, but just a short walk from an S-bahn station. We were in town for a big show at the fairgrounds (Messe) and this was really convenient, because we could just jump on the S-bahn that takes you right into the middle of the Messe. There were dozens of restaurants nearby, and lots of things to see and do in the evenings.
The breakfasts were really great; one less thing to worry about. Really nice servers, great attention to cleanliness, and responsive staff.
I will plan to stay here whenever I come to Frankfurt.