I understand your temptation, I really do. Big cars offer crazy value for money - if that was a C or E sized car on that mileage, it would have been sold by now.
Engine size isn't an issue if you're not going to be "working it."
But wouldn't the beautiful, elegant, W220 would be a better buy for the same kind of money.
You'll be able to pick up an S320 or S280 for similar money, in glorious condition, and better colours. 8-10 years younger, with much fresher tech, and so elegant.
Here's an example at £3,800 (call it £3,250) - but there are many around.
You'll be able to knock 20% off the asking price. Large cars don't sell in days or weeks - they take months or years to sell. Just take your time and buy a good one that doesn't need immediate servicing, tyres or repairs.
(Personally, I'd buy a 2005 low mileage, 2 owner, high spec car with main dealer history for £5k, but each to their own)
2001 Silver MERCEDES-BENZ S CLASS 3.2 S320 4dr for sale for £3790