We're not an overly large organisation (around 3000 end user devices and about 180 servers) but we are quite spread out over the regional area with some 46 different sites.
Luckily we are fairly well connected with majority of our network links being 10Mb, 100Mb or 1Gb
Microsoft's recommendation of best practice is to use the smallest number of sites as possible so I decided in the end to go with one central site and just add Distribution Points or Branch DP's as needed during the implementation.
Another decision I had to make was whether to go with physical hardware or go against Microsoft's official advice and virtualise it.
Well I kind of went half way.
I decided to put the Central Site server on our VMware ESX 3 Infrastructure and locate the site database on our physical shared corporate SQL server.
I was sceptical when looking at the recommended specs if it would handle it but I have to say I'm really surprised at just how well it does perform.
Since doing this Microsoft have changed their policy on virtualisation support (which isn't surprising since Hyper-V has been released now) so as long as the problem can be replicated it's now a supported design.