Considering I don’t often use Photoshop anymore, I generally feel quite lost in it. I now switched to Pixelmator for most of my needs. However, when I started on this site, I ran into a small problem - the guides were horrible to get right in Pixelmator. Some Googling later, I found this amazing plugin in for Photoshop. GuideMe allows you to enter the margins, gutter, column/row size and how many of each you need. It will generate the guides automagically. So for my sprites, I cheated and used Photoshop together with guideguide.me.
Here you can see it in action: