I would say Clarke Quay. Sorry to Orchard, but Clarke nowadays is better.
Park Regis is my favourite hotel in this area, but you've to cross the Merchant road (so it's like 3min walk to Clarke itself) - the Swissotel (Merchant Court) is good too, and the Novotel on the opposite site isn't bad either.
Location wise, Swissotel is the best of those three, but all of them can't be faulted. Furama is also not far away, and not bad location either. In fact, there are about 10 hotels close enough to CQ to walk that it's hard to choose.