Chew - Great little series with a fantastic premise. Set in a grim What If? style present scenario where bird flu killed millions of people. Eggs and chicken are banned, leading to the FDA becoming the most important law agency on the planet. The main character, Tony Chu, can experience the life story of anything he eats. So if he eats an apple he can experience it's beginning as a seed in the ground, to growing into a tree, to growing into an apple and being packaged. Great premise, good writing. Overall fun.
Ultimate Spider-Man/X-Men/Fantastic Four/The Ultimates - If you want to jump into the Marvel world without having to read any back issues, the Ultimate line is perfect. It's a reboot of the Marvel world, except not. The new stories exist in a parallel universe, so the previous universe is still intact. I recommend Ultimate Spider-Man, definitely the best of the series and some of Bendis's best work.
Y: The Last Man - Every single man in the world dies. Every baby in a mother's stomach, every full grown man and every animal with a penis dies, except for Yorick Brown and his pet monkey. The story follows him and two women (an agent and a scientist) as they try to figure out why he's immune, and how to save mankind.
Marvels - Probably one of the best comics I've ever read. It chronicles the first years of the Marvel universe, through the eyes of a reporter. No backstory needed (although a love of the Marvel universe will help you enjoy it more) as the story covers the very start of the first heroes, such as Namor, the Fantastic Four and the original Human Torch. Great read.
Kingdom Come - A DC title in which the heroes of the future are violent thugs. The original great heroes are old and disillusioned, noteably more weaker in their old age. The plot is told through the eyes of an ex-preacher, and his mystic guide. The big three DC heroes are forced to save a world which no longer wants them. The artwork by Ross is amazing, as always and Waid really brings out his A-game to write one of the best DC stories going.
Astonishing X-Men - If you're feeling like forking out the £40 needed to get the entire, hardback omnibus edition then this is a definite must have. Little to no back issues required (in fact, what little you do need to know is recapped in a handy guide at the start) and a fantastic story. Written by Joss Whedon (you know, the guy that did Buffy, Firefly, The Avengers...) with great artwork from John Cassady, it deserves it's recognised status as one of the top comics out there.
Honourable mentions go to All-Star Superman, Batman: The Long Halloween, Superman For All Seasons, Superman: Red Son and Batman: Year One.