I have used hand-painted or hand-dyed yarns a few times and I have run into problems by not alternating. It wasn't so much a question of pooling as the skeins of yarn being slightly different colors from one another. In particular I am thinking of a couple of projects I worked on with Alchemy yarns. They don't have dye lots, but I bought the yarn at the same time. In a group of 8 skeins, for example, 2 had more blue than the others, one was lighter than the others, and one was darker than the others. Alternating did help, it's no biggie to carry the yarn up the side, just do it loosely. But it didn't fix the problem completely because there were more than 2 color patterns, and I wasn't about to have all those ball attached alternating 3 or 4. So sometimes alternating between light and more blue, then sometimes between dark and more blue, and sometimes between dark and regular, etc.
Same thing with the Coachella I just made. If you go to the Whatcha Knittin forum, you can see in my evening Coachella each time I changed yarns. Starts off lighter, then the next skein had more mottling in it. The next skein was light again, and the last was darker than the others. I couldn't tell they were this different just by looking. They all looked gray to me.