What is the big difference between flat and dome top pistons? Which is the best or does it matter on the use. It's going into a weekend driver with some long trips.

You didn't mention whether you've got a small or big block. SBC's usually have plenty of compression for street use with flat top pistons, while BBC's need a little pop-up, especially with open chamber heads. It also depends on how much you're willing to pay for gas.

Sorry, I also forgot to mention that im looking at a 350/400 hp flat top, and the other is a 396/400 dome top.

Are you saying that you're deciding between a small-block or a big-block? That's a way bigger issue than piston domes.