It's probably more a personal choice thing as long as you find a combination a particular muzzie shoots well.
I started shooting black in 1970/71, and have always only shot real powder in mine. Works fine for me either hunting or at primitive matches. So I never had any desire to use the substitutes, in part because black gets in done very well and in part because they are not traditional to me. Goex was my standard, but I have also used Swiss when I could get it. For the 36's and 54, 3F was the choice for my 36 Squirrel and 36 Hawken, 2F for hunting with the Renegade, but 3F for target shooting with it. I only shot 32, 36, 45, 50 & 54 calibers and 12GA, so I figured when the 2F ran out I'd only buy 3F after that.
FWIW - YMMV