I'd like to add/clarify on the multi-card thing, a lot of older boards won't run at 2x4, but will run at either 2x8 or 1x16 (a lot of the first and second generation SLI and CrossFire chipsets (meaning nVidia/ATi made chipsets) work like this). The Asus linked does 16+4 which with 2.0 PCIe isn't much of a problem (the quick'n'dirty is that 2.0 PCIe doubles bandwidth over 1.x, so x4 2.0 = x8 1.x), but with 1.x PCIe can be a bottleneck depending on what you're doing. For non-gaming cards even running at x1 is not a problem (even for running Windows Aero Glass). To give you an example, I've run my GTX 660 at x2 2.0 and the performance penalty vs running at x16 is negligible outside of synthetic benchmarks; I'm not saying there's a good reason to avoid running at x16, just that it isn't the end of the world if you're doing multi-card and run with less lanes.
In general if you want to go with CrossFire/SLI you should look for a board that will give you 2x8 or 2x16 though. And given that you have the benefit of shopping used, I'd probably just go for a board that supports it out of the gate - keep in mind on LGA 775 that you have to choose CrossFire OR SLI; nVidia chipsets will get you SLI, ATi or Intel chipsets will get you CrossFire (this does not mean you cannot use an ATi card with an nVidia chipset or an nVidia card with an ATi chipset; just that you can't do the multi-card). X58 and later will do "both" (not at once), but that isn't LGA 775. If you want to go with CrossFire I'd go with an Intel chipset over an ATi chipset. As far as motherboard brands - Asus is a good choice; I'd also consider the Intel box boards (especially the "Desktop Extreme" models).
Honestly I wouldn't be intimidated by PCIe - it's silly simple to work with, and honestly I don't miss AGP since migrating.
On the Core 2: they generally don't run terribly hot, especially if you allow EIST (their power saving/throttling feature) to be enabled. The stock heatsinks are acceptable - apart from a heavily overclocked QX6850 or something you shouldn't have to worry, but an aftermarket sink will potentially be quieter (that was my primary reason for switching).
As far as what graphics card to get - I'd say it depends on what kind of power you need. I like the GTX 295 suggestion, if you need that much 3D power; if you just need something that will run Aero Glass, handle HD video/Flash, and be quiet and capable I'd suggest the GeForce 8600 (or the Quadro variant, the FX 1700). There's plenty of other good cards in-between those, but keep an eye on the pricing - spending $100+ on an 8800 Ultra or 9800GX2 probably doesn't make a lot of sense unless you specifically want that model for some reason (e.g. as a collector's item). You may also consider older professional cards - in some cases they can be a decent value or come in better physical condition than a gamer card, but be sure to check the model # against Wikipedia or similar to see what the "consumer variant" is (the numbering scheme for Quadro makes next to no sense, and it's a paragon of logic compared to ATI's naming scheme for pro cards) before you commit to one.
Something else you might consider, depending on your performance needs and curiosity level, is getting a "basic" SLI or CF system just to play around with, like a pair of 8600s or 3650s or something. Sure, back when they were new it wasn't a great value proposition, but as cheap as most of the mid-range cards are these days it shouldn't be too much of a problem to track down two, and you could toy around with it without needing a massive power supply or huge cooling capabilities.
One final note: do not bother buying Quadro FX cards to do a DIY SLI setup - nVidia explicitly locks the feature out except for OEM partners (the shortlist is Dell, HP, Fujitsu, and Lenovo); if you bought a motherboard from a certified system it would probably get you around that, but it may have its own associated quirks (like being a proprietary form factor, having limited BIOS options, etc). I don't remember AMD being as restrictive with CrossFire Pro beyond it still requiring the system to support CrossFire.
