My tuppence from living a few miles from the bottom of Hardknott...
Fred Whitton-wise, the obvious shortening is to remove Newlands and Whinlatter. However, don't underestimate the smaller climbs - Fangs Brow, Cold Fell and Irton Fell all add to the general battering!
Also worth thinking about direction. IMHO Hardknott is more of a beast from the east, and Wrynose definitely is!! Therefore, riding from Coniston to Eskdale is harder than Eskdale to Coniston. For the extra burn, start up Langdale!
Descents on the steep stuff tend to be less than pleasant, though Honister into Buttermere is cracking after the first steep bit ad Wrynose is good either way. The top section of Honister (Buttermere side) is notorious for nasty crashes on the FW, think steep rutted tarmac and sharp stone walls!
Off the Fred Whitton route and further from muppets who can't control their cars:
The climb out of Ulpha in the Duddon, over Birker fell and descent into Eskdale are fantastic.
Corney fell from Duddon Bridge over to Waberthwaite ish gives awesome climbing and descending in both directions, with the sudden view of the coast as you reach the top after climbing from Duddon bridge being particularly special.
Both of these can be combined with Hardknott/Wrynose to give excellent adventures.
Finally, if you're on the back lanes north of Cockermouth/Keswisk, I think there are still a couple of bridges missing!