From what I am seeing, each successive Intel chipset from the 875P upwards has been handling 4 DIMMs better and better than each predecessor. There is not near the performance hit there used to be. The 680i chipsets seem to a little more finicky to tune and require a bit more voltage bump but it is not hard to do with a bit of patience.
And, latencies don't seem to matter so much on C2D. So, you can run a PC6400 2 x 2gb kit at about 1.8 to 1.9v while OCing the CPU to 400+ FSB. Most people don't go too far past 400FSB anyway.
That said, it is still easier for the "average" guy to simply plug in 2 x 2gb DIMMs, run stock voltages on the chipset, and have his system run longer with less voltage and heat. OCers are an entirely different animal. There's no wrong answer here and currently, 4 x 1gb is a bit cheaper but not much.
And, chipset limitations are not the only factors to figure into using 4 DIMMs. Consider you will likely need better cooling and in some cases aftermarket cooling on the chipset depending on the board you get. Longevity may play in so your MOBO might "only" last 4 years OCed instead of 7 with stock chipset voltages. The system will consume more power and there are 2x as many DIMMs to fail.