I will be baking 18", 14", 10", and 6" rounds for a tiered cake using the cake stackers system. We want to use the Cake Boss white velvet. I do not have any concerns about the two smaller layers but wonder if I should use a denser cake recipie for the larger layers. What is the rule of thumb for this?

The cake tiers aren't supported by the other cake tiers but by the cake support system. So you can make any type cake you'd like they'll be supported by the cake stackers system.

Although you might want to research the SPS system (very safe and secure, but more reasonably priced):

http://cakecentral.com/cake-decorating-ftopict-603925-sps.html

HTH