Hey GTA people. 
Got this issue with GTA IV, patched 1.0.4.0 running on: 
Windows XP x64 SP2 
Gigabyte ep45-ds3 
Core 2 Duo e7400 OC'd to 3.15GHz 
2x1GB Patriot Viper 1200Mhz DDR2 
Radeon 4890 1GB OC'd to 950MHz / 1050MHz 
160 GB WD SATA 7200 
Genuine system / game 
Got plenty of free space on HDD, set page file to 4096MB, got newly installed system, defragmented and all that, other games work very well (Crysis, FSX etc) 
I start the game, it works well - got approx 30fps min with highest settings. After 10-15 mins the "nightmare" begins - game freezes for like half a second and the hdd spins like crazy.  
Then it unfreezes, goes well for few seconds and freezes again. Over time the freezes become more and more frequent and as a result game becomes unplayable after 20-25 mins. 
Would you guys know the best solution for that? (Hope you will not say "buy more ram"  )  
Oh, forgot to mention that i tried reducing the graphics settings to minimum with resolution 800x600 - not helping. 
THANKS