The short version
Base in the City Bowl or the Atlantic Seaboard (Camps Bay / Sea Point). Avoid a Waterfront-only stay unless you specifically want the mall-and-hotel compound — it's convenient but it's not Cape Town. Two neighbourhoods cover 90% of trips; pick by vibe, not by star rating.
City Bowl
The centre — walkable to restaurants, the Company's Garden, Long Street, and the cable car. Best for first-timers who want to feel the city. De Waterkant and Gardens are the quieter pockets; Long Street itself is loud at night. Good for a stay-without-a-car week.
Atlantic Seaboard
Camps Bay and Sea Point — the beachside, sunset-facing side of the city, 10 minutes from the centre. Prettier, breezier, more expensive, and the right call if you want ocean views and a slower evening. Clifton if you want a beach and no traffic; Sea Point for value and walkability.
Southern Suburbs
Constantia, Newlands, Bishopscourt — greener, quieter, close to the wine estates and Kirstenbosch. Best if you have a car, want space, and plan to spend days at the mountain's base rather than the waterfront.
Don't
Don't base somewhere you wouldn't walk at night — ask before you book. Don't stay out in the northern suburbs if your days are the city and the mountain; the commute eats your trip. And don't change hotels more than once in a Cape Town stay; the city rewards a single base.