Not familiar with skulltrails.. but with the Core 2 Duo, I usually run 2 monitors.. both HD.. running 2 NVidia 8800s in SLI, I run Windows Media Center with my TV tuner on 1 monitor and play Age of Conan with the other. no issues at all.. I even split my audio.. Primary sound for game off my 5.1 surround, and have my headphone jack set up on 2nd audio output with desktop speakers connected for full stereo sound.
I know that my NVidia's are designed to run 2 monitors in HD (Dual Link DVI) x2 cards.. so a total of 4 monitors without a single glitch on Windows 7.
Only limiting factor is system memory.. so definately recommend 64 bit OS with 8 GB system memory and recommend the i7 CPU @ 3.0 Ghz (3.2 GhZ preferrably) and at least the 960 chipset (preferrably the 980 chipset for overclocking later on to pull more system performance to compete with newer hardware that will come out)
I truely don't see a problem with Windows 7 (with ready boost enabled) and NVidia cards and running multiple monitors.. the NVidia driver control panel has Multi Display or single display operation which is selectable so setting up for Multi-monitor will actually expand your settings to each monitor and allow each video port to operate separately.. now how Windows 7 handles it, I just expand my desktop to each monitor and drag / drop each program to each monitor and allow the GPUs to sort things out on their own.. but I get no lag .. however remember the more memory intensive the application, the more system ram and the stronger CPU and the better the vid cards you need.
but the i7, 980 chipset and 2 NVidia 295 GTX with 1.5 GB vid memory each, and 8 GB system memory and 8 GB ready boost - you should be able to push 4 monitors in HD, or 8 monitors in VGA (using adapter from Dual Link DVI to VGA and then a splitter).. the vid cards I mentioned can handle that task with no problems if you are running 4 monitors.. the OS should be stable enough.. so the remaing factor is the system itself.. however any CPU / Motherboard still using FSB will introduce unnecessary latency due to speed limitations (slower clock cycles in the CPU).
Now as for Multiple Cores.. Windows 7 optimizes programs for CPU usage, however at times some programs may not utilize each core properly (not Windows fault, but application programming error) you would have to set CPU affinity manually in Task Manager opened in Administrator mode.. but you can actually set each processor to different tasks.. like CPU 0 (primary) to OS, CPU 1 to Application A, CPU 2 to Application B and so forth.. or you can just set affinity for all programs to all CPUs and allow Windows to equally distribute CPU processing power to each application.. that is up to you.