My 2c, for what it's worth.
I run SME from home as an after hours job that I can make a little bit of money here and there. I run several websites on it for people, and run mail and a couple of other small services. It just runs and runs.. I once had an uptime of 282days, until I learnt about the problems that you can have if you don't keep your system up to date with security patches.

Now I update when there is updates waiting.
My day job sees me working with several M$ Server 2003 boxes. I think the major differences I see is:
- The cost, we have to pay for most software. We haven't even gone with Exchange because of its cost.
- SME is so much easier to administer. Through the Server Manager you can do most things. We can spend a fair while on a M$ box trying to find where they put stuff.
- It's also easier having less options in your face. On a M$ box to setup another website can take a fair amount of work, ticking and un ticking boxes. Then lining up IP addresses so they can be seen on the outside world getting the DNS right etc.
I have setup an SME box at a school I help out with. The reason I went with SME was firstly because they didn't have the money for Server 2003, secondly, they wouldn't know how to operate Server 2003, and they don't have an onsite tech. SME can be administered by any tech savy person that knows how to use a website.
Why I chose SME over Distros - I've used others, and there is nothing I've seen that out of the box, just works with as many options etc as SME. Esspecially the mail server, I've never seen a mail server so easy to get up and running.
Cons - You can't run several SME boxes at once all using the same DB for user and group information. If I was to use this on a bigger scale I'd like to be able to run a couple of login servers over a campus. Also the option of separating a couple of services onto different boxes like Web, Proxy, and Mail. But in saying this. If the box is powerful enough (no some old piece of resurrected scrap) it will handle all these services on one box no worries.