The most circuitous seems to have always been Cheltenham. Even the GWR's fastest train "The Cheltenham Flyer", was a complete misnomer as the speed run was between Swindon and Paddington. Out of Cheltenham it was hauled by a tank engine to Gloucester in exactly the opposite direction to London; I think after an hour's travel it was no nearer in a straight line towards London than when it started.
But the most difficult place to get to from London is undoubtedly Workington/Whitehaven in West Cumbria. No main rail service, but there's no airport either, and it's a huge drive. The nearest practical rail station is Penrith, from where a taxi will set you back the best part of £100. It's far more straightforward to get from London to the main Scottish cities.
Colleague in London asked me what was the nearest airport to Workington. I said Isle of Man

(which is true; with binoculars you can see aircraft approaching it).