If you're looking for the absolute best performance, it's often suggested that you use all the same size DIMMs. I know that on the Mac Pro, there is an optimal way to use the 8 slots on the two memory risers. I'm not that familiar with the iMac, but a little research on the Apple forums should find the best pairings. On the Mac Pro if you use 4 DIMMs that are of the exact same size and speed, the system will be able to burst wider bus access when filling the on CPU caches. That of course results in faster execution of programs etc.
BTW, if it's a new iMac, it will come with 64 bit Snow Leopard, so David's question about RAM size above 4GB isn't relevant. I currently have 16GB in my Mac Pro running the same OS and it often can use it all!
And on a side note, I strongly recommend OWC (Other World Computing
http://www.macsales.com) and Memory to Go (
http://www.memorytogo.com) for your Macintosh memory needs. All 5 of my Macintosh machines have memory from one of these two companies.