I've already tested both 500GB drives with Western Digital's own diagnostics utility. Both drives report a good SMART status and neither has a single bad sector, using the full scan. Chkdsk also reports no bad sectors or any other problems.
I used to have 4x1GB sticks of RAM, but that combination gave me lots of headaches with this motherboard (memtest errors, random boots...), so they got replaced with 2x2GB sticks and now all those problems are gone. Except for TQ.
Everything hardware-wise has been tested with either a program or by changing components; RAM, hard drives, motherboard, dvd drive, keyboard, mouse, monitor. Well, CPU and power supply i haven't tested, didn't find spare parts for those in my box-o-pc-junk. If the power supply were at fault, like random surges for example i'm 99% certain i would see problems with other power consuming games or applications.
I greatly appreciate the suggestions, but i'm slowly beginning to think it's just Titan Quest screwing up. After all, this isn't exactly the most bug-free game ever made. Fun and entertaining for sure, which is why it hasn't yet been uninstalled despite this.
I've also fiddled with nVidia's driver settings, filterings and anti-alias etc. and TQ's settings, but no matter if enabled or not, whatever resolution is used... it always does the damn thing.