Do you prefer to go with similar choices on balls and use significantly different layouts to create your differences, or do you use similar layouts and use ball choice to create your differences, or a little of both?  I really don't get too creative with my layouts, admittedly because I really don't bowl on anything that forces me to.  I also feel like ball design is going to dominate layout, and something else that feels silly to me is when people pick a ball, and then a layout to counteract what the ball was designed to do.  Like picking a skid/snap monster and wanting to go 40x4x50 to "smooth it out a bit."  But again, I do what works for me, and for everyone else what they want or what works for them.  What works for you?

I try and matchup the ball for the condition, and then the layout to help make that work.

" Like picking a skid/snap monster and wanting to go 40x4x50 to "smooth it out a bit." 

That layout for most the ball will still skid snap. Adjusting the surface can tame the backend reaction a lot easier. I recently drilled a Melee 2.75" x 45 with a flare increasing x-hole. The videos of the ball at box finish have the ball being extremely long and with just a little finish down lane nothing jumpy. Sounds great but, my normal 5" pin range of layout will likely make the ball almost useless to me on most conditions other then really broken down or drier. After testing the ball it has the same characteristics as seen online but it pickups just a little sooner with a  little stronger backend. The layout can not over come the surface of what the ball is wanting to do.

Just like drilling a dull hook monster to go long and snap, or a plastic ball to roll early the ball surface and intent is the bigger factor.

Matching up the ball to the condition, then the layout to the ball for the bowler is the ideal way to go. (Customers have no clue what that is)