According to a stats book I have from the late 1980s, after Hull the next largest town/city never to have had a Division One club (top flight) is Plymouth. According to that book the population of Hull was 280,000 and Plymouth 250,000. Obviously, those figures will have changed, but I guess it's still Plymouth.
Worth pointing out, it has often been reported that the City of Salford is the largest never to have had a League club. United play in the metroplitan borough of Trafford which is neither in the city of Manchester nor city of Salford (though a lot tend to think it is).
The A-Z of British Football Records (produced at various times in the 70s, 80s and early 90s) claims:
Salford (150,000) is the largest separate town (i.e. excluding London boroughs) never to have had a League club, although Manchester United play right on its border.
Elsewhere it states that there are 3 clubs that play outside of their 'home' town - Nottm Forest (West Bridgford), Grimsby (Cleethorpes) and: Manchester United's Old Trafford was (and still is) in Stretford. Obviously, since then other clubs have moved.
Another odd stat - according to that book Bristol is the largest major urban centre never to have had any of its sides win a major trophy. It did also say Middlesbrough, but that's happened since.