A 1366 board will use ram sticks in 3's. 1156 uses sticks in pairs. Given that you've said there are four slots, I'm assuming an 1156-based board. On a personal level, I'd likely put in two sticks of four and see how 8 travels with you, unless you simply want to fill the board slots in one go. I'm told that 12gb is fairly sufficient for any use as the Win7 image unpacks into about 3gb running. I'm seeing 4 personally, but I've not bothered with optimizing at all at present.
RAM/GPU, and this goes for anything that needs to traverse a physical interface, will always slow down processing when compared with something inside the CPU. It's just a question of how much. PCI-e describes the interface speed so nothing to fret over there. Memory can be a slow-down issue but I've tended to find that it's more a question of amount of ram, as compared to speed of ram. (more ram = more cache = less paging).
580 is the current top-end (590 is a factory overclocked 580 afaik) and is the natural pair for the 58X motherboard. Pricey though currently (bleeding edge describes your wallet, not performance). If you want a bit of upgrade insurance though, it's the way to go. 480s/580s in SLI is fairly heat-intensive though, so make sure to get a nice case with good flow, or water-cool. (I mention this to frighten you, not to encourage you to go through the two-week headache I just did). Water-cooling is expensive and a royal pain to do.
Chipset upgrades these days have more to do with micro-code optimizations between procedures handled by the cpu and those handled by the GPU, performance gains are marginal, meaning that the bigger the margin of upgrade, the bigger the performance boost you'll notice. By way of personal example, my upgrade was from Pentium D-based to i7. I noticed it a lot. If I'd had a dual core, I may not have noticed it to the same level.
On the whole, if you're playing something that really dogs your hardware (like Crysis 2, for instance), you'll notice underpowered hardware lags and poor quality in video. If you're just playing Eve, you'll be able to turn on all the shiney graphics and still be locked into 60 fps (unless you un-restrain the wait intervals)