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The centre is small enough to walk across in half an hour, so location matters less here than in most cities. What it costs matters far more, and it moves violently.
The one thing to check first
Manchester has two Premier League clubs, the largest indoor arena in the UK, a second major arena, a big convention centre and two large universities.
A home fixture, a stadium concert, a conference or a graduation weekend can double or triple rates across the whole centre. So can the Christmas market season from early November.
Check the fixture list and the arena calendar before fixing your dates. Shifting a trip by one weekend saves more than any other decision you will make about this trip.
The districts
Northern Quarter — the most interesting part of town, the best bars, and genuinely loud until three at weekends.
Deansgate and Spinningfields — the newest and best-appointed hotels. Corporate, and much cheaper at weekends than midweek, which is the reverse of most leisure destinations.
Piccadilly — cheapest central option, and next to the station. The gardens and station approach have a visible street-drinking problem. Not dangerous; not pleasant.
Ancoats — the best restaurants, quiet at night, mostly apartments rather than hotels. Fifteen minutes’ walk in.
Salford Quays and MediaCity — cheaper, on the tram, home to the Lowry and IWM North, and very quiet outside office hours.
Chorlton and Didsbury — where Manchester lives. Better value, real neighbourhoods, and a bus or tram every time you go into town.
The full comparison is in where to stay in Manchester.
Apartments
Manchester has an unusually high proportion of serviced apartments and aparthotels, because of how much residential tower building has happened in the centre. For three nights or more with a group they are usually better value and give you a kitchen.
It is worth knowing that short-let conversion of city-centre flats is a live argument in a city with real housing pressure, and that a stay in one is not a neutral act.