Burnout Paradise City- Very fun game, lots of free updates available and only $20, can't go wrong. IME you don't have to be a fan of racing games at all to enjoy the Burnout series, they are just a lot of fun(although Paradise City may seem a bit overwhelming at first with its' open format).
Street Fighter IV for fighter- Noone else has mentioned this yet????
Killzone2 if you are a shooter fan- comes out Friday, looking to have a solid single player game and some killer MP action. It also packs the most visual punch of any game this gen on any system(if that matters or not, it's still a very fun game from what we have seen in the demo).
Little Big Planet if you like old school platforming
Guitar Hero is a blast too, I picked it up because my wife really wanted it- the kids all love them on the other systems- and found that I really had quite a bit of fun with it too(even if my son can thoroughly stomp my @ss into the ground

).
How about if you've never played a MGS game?
MGS has never had anything better then mediocre gameplay, it's story/cutscene driven, if you aren't a fan of the series I find it highly unlikely MGS4 would give you anything but an absolutely terrible impression.