There are only two limits you have to watch out for when working with the datastore, and they're both fairly well documented:
* You must be careful of entity group boundaries. This ends up being fairly easy to do, especially with cross-group transactions (added last year). It's definitely a design consideration, but one you internalize very quickly and as long as you don't screw up your database design, isn't a scaling bottleneck.
* Tablet splitting. If you write monotonically increasing values to one index at high rates (1k/s is what I've heard, but I haven't hit it myself) you may have to work around this issue by federating the index. It's not pretty, but it's not a common problem.
I agree that traditional RDBMS architectures can handle quite a lot of traffic before they hit a wall. It's just a lot more ops work. What I like about GAE-land is that you just have to be a little more careful in your data modeling and you can stop worrying about all the usual problems like monitoring the performance of your database server. I've built rather large sites on RDBMSes in the past, and getting the ops right was always painful.