I always cut against the grain when I can. It is easier to chew the short fibers opposed longer fibers when meat is cut with grain. But…………..If brisket is taken to 200-205 deg F. It is vey tender no matter which way it is sliced, especially if it is cooked low and slow…
I do notice a huge difference when grilling Tri-tip @ medium -medium rare. If I forget and cut with the grain it is much chewier than against the grain. I always try to cut against the grain if possible..