1. Inherent Vice: read this one first. It's a crime novel set in a slightly exaggerated version of 1970's LA. It's full of stoners, groovy language, flower power with a crazy missing persons plot. Its got lots of pop culture references that anyone should be able to get if they've been paying attention at all for the last couple of decades. It's more or less Robert Altman's Long Goodbye crossed with a Cheech and Chong movie...
2. The Crying Of Lot 49: after reading Inherent Vice you should be able to handle Lot 49 which is basically set in the same milieu and is only a little bit weirder and more discursive. The plot roughly revolves around Oedipa Maas who has possibly uncovered a secret war between two clandestine postal delivery companies. Yes, it's that sort of book.
3. Bleeding Edge: a paranoid shaggy dog detective novel set in the Manhattan of 2001 just before the 9/11 attacks. It begins with a Westlake quote and its a spicy blend of Westlake, Hammett, DeLillo and Woody Allen. (With a David Foster Wallace cruise ship homage thrown in there for good measure.) It's pretty funny and it concludes a thematic trilogy of sorts of that began with Inherent Vice and Vineland.
4. Vineland: America in the early 80's. Reagan, Star Wars, George Lucas, Brock Vond. And again most people should be able to get the refs. As I say Inherent Vice, Vineland and Bleeding Edge form a kind of paranoid alternative history contemporary trilogy that should be accessible to most general readers.
5. Gravity's Rainbow: Pynchon's WW2 novel which won the National Book Award. His best book? Probably, yes. It's quite a difficult text but by no means impossible to read especially in a trade paperback edition with big clear print. You'll need to know your mid twentieth century culture quite well to get all the refs this time. And just to warn you, amidst the humour and horror there is a pretty gross scene involving coprophilia.
6. V: my favourite Pynchon. A literary romp through early twentieth century history. Very abstract, strange and off putting for the uninitiated. But a great read once you get the momentum of the story.
7. Mason & Dixon: the story of Mason & Dixon surveying the land that will become the North and South of the USA. This is my second favourite Pynchon. It's written in eighteenth century prose so it could be tricky for some people, but not for those with Clarissa, Tom Jones or even Neal Stephenson under their belts.
8. Against The Day: This is possibly for completists only. A dense, difficult, but often very funny story of turn of the century America. My favourite scenes were set in a beautifully crafted wild west Denver.
Additionally: Mortality And Mercy In Vienna, a strange out of print novella that I read in the Columbia University stacks before it got stolen and Slow Learner a nice collection of short stories, the highlight of which is probably Entropy.