I work for a CDN (just the same as Akamai), and I'd like pass some knowledge along.
When an anycast (
http://en.wikipedia.org/wiki/Anycast [Every CDN depends on anycast]) based DNS system is used, you are load balanced to a nearby POP/node/cluster (whatever you want to call it.) The idea behind this is to route you to a very close (geographically that is) server that will be able to return the desired data to you as fast as possible. In making the connection as close as possible, you reduce the possibility of introducing unnecessary latency. Currently, the speed limit is the speed of light (based on use of photons in the fiber links). Until we find a way around this, bringing the server close to you is the next best option.
So, with anycast already mentioned, the next part of this is the load balancing. When you use something like 4.2.2.1 (and it's relatives), OpenDNS, or Google DNS, you are relying on a system that is making a best attempt at determining where you are. If it works as intended, nothing goes awry. If it there is a fault, then you may get routed to a server that is quite far from you (geographically, as well as latency-based.) This can occur if you use OpenDNS in London, UK, and you get routed to a server in New York, NY instead of somewhere in England. This can cause for a slow internet experience, which generally sucks.
If you use your ISP's DNS is that you can be much more certain that you are being routed to a set of nameservers that are close to you, and can generate a quicker response to your queries. The added bonus of using your ISP's DNS is that a CDN such as Akamai almost certainly has a POP (or cluster, etc) located inside of the ISPs network, and so when you get load balanced to the CDN (instead of the DNS), you are hitting servers that are not only close to you, but don't have to traverse the internet's main backbones. This means you get what you want very quickly.
When people use an anycast based DNS system, and complain of slow load times, they are almost certainly being routed to a POP that is either far away from them, or is just overloaded (or both.) I've run into this myself when attempting to retrieve updated Apps from the iTunes App Store when using 4.2.2.1. When I changed my router over to use my ISP's DNS (in this case, Road Runner), the files came in at the max speed my connection would allow.
If you use an anycast based DNS, and are encountering a less than great internet experience, I encourage you to switch to your local ISP DNS. Things should be much better as a result.
I hope this helps shed some light onto the situation.
Cheers.