I have used several different grade book solutions in my many years of teaching. In the past my favorite have been applications that are directly installed on my computer, but the one that I use now and don't foresee ever leaving is web based. I have used very expensive online solutions adopted by our district such as PowerSchool, but the interface seems to be an after thought. In my opinion the best option out there at any price is Snap Grade. It is very well designed and easy to use, but it also has many powerful features that make it perfect for about any situation.
Snap Grade's interface is probably one of the best thought out of any grade book I have seen out there. You enter the information about the assignments on the same page you enter the scores. It took me about 20 minutes to set up all of my students and classes and have the first scores entered. It was intuitive enough that I didn't even need to look at any of the help documents. I did have to look a little to find a way to do a missing assignment report, but everything else was pretty easy to figure out. Being web based, it is available from any computer, but they wen a step further and built a Mobile interface so it can also easily be used from an iphone, ipod touch, or android based phone. The mobile interface is not quite as easy due to limited screen real estate, but it is well designed. It is great to be able to wonder around the room and checkoff journals or spelling on my iPod. If you want a few more advanced features and the ability for parents to log on and view their child's progress, you pay a relatively low price of $49.95 per year. They also have options for group discounts the allow for school wide administration, and reports. If you don't need these additional features the application is free. It is free to sign up and try it out and it is well worth the time to try it out.