The higher voltage/lower kv setups are going to run longer and more efficient. As others have stated, as you go up in voltage you should be running lower mah packs that are going to weigh about the same as the lower voltage higher mah packs for the same runtime.

I ran 4s 5000 setup earlier this year and I get a few more minutes run time with my 5s 4000 setup (geared for the same speed) under race conditions. The 5s 4000 pack is slightly heavier, but not enough to make a difference in how the car handles. I get SUBSTANTIALLY more runtime with a 5s 5000 pack vs a 4s 5000 pack even though the 5s 5000 pack is SUBSTANTIALLY heavier.

You don't have to over complicate it. All I do is go volt & mah to get energy in pack and match that you want to run. Verify that the higher volt pack is reasonable weight and go have some fun.

14.8 * 5000 = 74,000 mah - Zippy-H Pack Weight: 529 grams
18.5 * 4000 = 74,000 mah - Zippy-H Pack Weight: 581 grams
22.2 * 3300 = 73,260 mah - Zippy-H Pack Weight: 529 grams

The 5s 4000 pack is actually a higher C rate pack. the 4s & 6s are 20-30c rated while the 5s 4000 is 25-35c rated.

The higher voltage will run a bit longer due to better efficiency even though the total energy of the pack is the same and even if the weight is slighty heavier.