Stay here, eat elsewhere.
I enjoyed my recent stay at the Manchester Grand Hyatt. My room in the Harbor Tower was spacious and clean. Everything was in working order (iron, tv, hot shower, a/c & heat). The wireless internet was fast and consistent for me - think I lost the connection once in my 5-night stay. Bed was comfy. I had a nice view of both the city and the harbor.
Cons: 
The hair dryer was a mini travel one - wish I had brought my full size.
Cobb salad from room service was pretty awful, and buffet breakfasts were overpriced (but that is expected at any large, corporate hotel). 
Tub faucet was coming away from the wall - I didn't complain, because it didn't affect me at all; but I'd expect better from a Grand Hyatt. 
It is a HUGE hotel with two towers. I came and went without anyone even noticing, there were no hellos from the doormen, etc. - but this is fine with me. Any staff I did encounter were incredibly kind and helpful.
In terms of location, it is a 7-10 minute walk down West Harbor Dr. to the Convention Center, and a 10 minute walk up Market St. to Horton Plaza and all the restaurants around that area. Little Italy was a 15 minute walk up Kettner. The hotel sits directly on the harbor, where there is a great walkway for running, biking, walking, etc. Very flat and pretty views.
I would definitely recommend eating away from the hotel. Go to the bar on the 40th floor for a spectacular view of the area, but then walk over to 4th or 5th or up to Little Italy for more afforable, more creative food.
Also - be forewarned that there are freight trains that barrel through downtown, blaring their horns at all hours (usually between 3-6 a.m.). This is hard to avoid no matter where you stay if you are along W/E Harbor Drive, but maybe ask the front desk if you could have a harbor-facing room to help dull the sound!