If starting from scratch with no knowledge of any of the games, I'd start with SR2. (which is where I began originally and honestly, I know nothing about SR1)
That was pure gangwar, mostly straight humour while a bit over the top and random psychopathy.
SR3 amped it up and made it more whacky. Was quite hilarious.
SR4 was more good stuff, mixed with the Matrix effectively and various aliens. The expansion to SR4 looks intriguing, in case it was unclear where the series could possibly go from SR4, given the way the 'world' has expanded with each game, from neighbourhoods in a city, to being the leaders of a huge media empire, to an alien invasion by a galactic empire and being put into the matrix.
I must confess to having been a bit bored at times in SR4, when it came to doing side missions - the main missions were okay, generally speaking, though super powers did make cars mostly pointless - not flying vehicles entirely though.
It just leaves GTA in the dust when it comes to being over the top, but GTA has its own charms in being more like a mostly-straight-faced action movie compared to the sci-fi superhero film that SR is by games #3 and #4.
