Nothing is sacrilege! Nothing is sacred in making music, all of it is aesthetic. If it sounds good, it is good.
Some people have totally lost the plot and will argue for hours about which exact manufacture you should buy your pickguard screws from if you want a True Vintage Authentic 1963 strat and if you don't get exactly those then YOU DONE RURNT THAT GUIT-FIDDLE, BOY! LORDY YOU JUST MADE THEM TONE GODS SRV AND HENDRIX DONE ROLL OVER IN THEIR GRAVES!
Don't listen to those idiots. Guitars, amps, and cabs are tools. They're there to make the sound you want them to make, not the other way around.
edit: tread more lightly if you consider resale value important, lol, but if A. you don't care about resale value, or B. you can revert whatever you change back to stock, it doesn't matter.
So don't be afraid to try 8 ohm V30's or Greenbacks in that Mesa cab if that's what it takes to get the sound you want. For a personal recommendation, I use EVH 4x12's with my 5150 III's and find that the EVH speakers (they're just relabeled Heritage Greenbacks) to be fantastic for 5150 style circuits. Heritage Greenbacks are basically standard M Greenbacks but they have a slightly smoother high end, which matches really well with a 5150's extended high frequency content I think.