On what game?... Maybe 2d games, but I really doubt it on games like FFX and others.
And yes, HDD speed rarely effects anything, things like PCSX2 won't be affected by it. Only reason why most people preffer to create ISO's of their games and run it off their HDD is because of that slight lag you get from the DVD-drive revving up to read the next portion of data. Others do it because their drives sound like Jet Fighter engines (like mine...last time I buy Lite-On grrr
).