Orchard Rd is the obvious choice if you want both a five-star hotel and "restaurant/cafe culture" on your doorstep; sure, it's touristy, and not quite 24h, but close enough. Four Seasons might thus fit the bill, although it's ever so slightly on the 'wrong' side of Orchard Rd.
Another option might be the Fullerton or Fullerton Bay. While the CBD is pretty dead at night, you can just walk up the river through Boat Quay, Clarke Quay, Robertson Quay etc for lots of nightlife and eating options; as a rule of thumb, the quayside joints are for the tourists and one street back is for the locals. Parkroyal on Pickering is in the same general area, and close to Chinatown as well, which also never sleeps (roadside frog porridge at 3 AM, anyone?).
I find the Marina district a bit dull, although there are more shopping malls than you shake a stick at with tons of eating options.