I'd say regions mostly make sense operationally (as they allow integrated services in a particular part of the country), except there is a good case for a return of NSE, particularly now cross-London routes such as Thameslink exist.
So, the divisions would be: NSE, Western, London Midland, Eastern, Scottish and Welsh (the last due to devolution, operating services entirely or mostly within Wales only). The Southern would of course be a subset of NSE.
NSE would be mostly like the "old" NSE, except I would transfer Waterloo-Exeter into the "Western Region", as it's the only diesel route into Waterloo and seems, to me, to belong to the same group of routes as the "regional" routes in the southwest. Compatible stock, too (159s can work in multiple with 158s and presumably 150s, etc). Perhaps, in fact, the entire group of Paddington mainline services (including ex-NSE routes such as Oxford and Worcester) would be part of the Western rather than NSE, as Paddington doesn't really have an extensive commuter network. The Elizabeth Line could become part of NSE.
Cross-Country would most naturally belong to the "London Midland" region as it's centred on Birmingham.
InterCity would also return as a branding, with its own livery, but individual IC services would be operated by the respective Region.