Steve, what is your intended purpose for the rifle? It's obviously going to single feed, and with a 29 inch barrel would I be right in presuming targets?
In my F class rifles I choose a bullet to shoot, predominantly the Berger 7mm 180 gr VLD, if it doesn't shoot I change the powder, luckily there's plenty of powders to choose from, getting hold of them is another matter.
With George's outline of what he set out to achieve with the 6.5 4S (which might not be yours) it looks to me like there's only two real choices of powder (in my opinion) those powders are H1000 and Retumbo, both are single base and slow burning, producing low pressure and generating good velocity and hopefully good barrel life. I will be happy to get 2K, let alone 3K of barrel life!
I did run V N170 through QL, but it couldn't generate the velocity, N165 could but then it went over 58000 psi, which is a pity as it's known as quite a forgiving cool burning powder favoured by many F class shooters using 7 WSM's.
So to me it looks like if something isn't working then selecting a different bullet would be the logical option? We're fortunate to have so many to choose from to suit the 6.5 Saum, I can think of at least eight between 130gr to 140gr.