The biggest difference between the 2 is in S3 the ram remains powered and holds the data, in S2 the ram powers off and data is written to the disk.
What changes in custom systems or even OEM systems with add in cards added is how the add in cards react to being powered down and interact with the system.
I remember adding a older Nvida card to a system years back that went in and out of sleep mode without issue but would not wake up with the card installed, remove the card and the system worked fine once again. Never did figure it out replaced the card with the same card and it acted the same way, replaced it with a ATI card the the system worked fine that's where we left it.