I personally use Microsoft Security Essentials on all of the machines on the network here. I've also locked down user accounts on most of the machines, most users are limited or Power users. There are a few exceptions, but I won't get into them here.
I use it too, and havent had any problems.
The big thing with Windows is getting your users to get used to not having admin privileges from the word go. A good firewall (the stock firewall in XP SP2 on is a good choice for the average user), and a good malware program are all you need. I've had exactly 3 false positives with MSE, and those were for programs that that customize other programs (and thus act like malware, so I want them to be IDed).
For Mac users, the issue is that they are so not used to being safe that they are at quite a risk.