My advice:
1) Get a few really good pairs of shorts. I found that spending a little more made a big difference.
2) Go to a bike shop, and see if you can test ride a few different seats. The size and squishyness matters a LOT less than the shape. If you get one that's the right shape for your butt, it will disappear under you, regardless of size. I have a skinny little narrow seat, and this weekend I rode 52mi on Fri, 67 on Sat, and 68 on Sun, and I have no soreness at all.
3) Like less'go said, seat adjustment. The height needs to be right, but also experiment with tilt. The rule of thumb on height is to have a freind ride behind you, and keep raising the seat until your friend notices your hips rocking. When your seat height is right, your hips will stay perfectly level.
Good luck!