Every time Edward's beauty is described, take a sip. If you're feeling adventurous, take a shot. If you're feeling suicidal and want life to end, read the book again and drink every time anyone's beauty is described.
Or whenever anyone is chagrined...
Or whenever Bella treats her normal human friends classmates like dirt for no reason (every time Lauren is mentioned, for instance)
Or whenever Bella bitches about something. If you're still sober by the end of book one, promptly start reading book two — same rules apply to all of the books, by the way.
Take a sip every time a dash is misused, and a drink every time the word "said" is NOT used to describe someone's way of talking talking.
Take a sip every time Smeyer uses a big word where it sounds awkward.
Two if its misused and out of context.
Take a sip/shot whenever Smeyer contradicts her own canon (ie, when Bella arrives, she complains about the scenery, then when she goes to la Push, she compliments it with tons of Purple Prose, then goes right back to whining about it later)
Take a sip every time Bella does something stupid and/or bitchy, and one every time Edward is being a bad boyfriend.
One every time he's shown stalking her
Down the bottle if she's actually shown flattered or pleased by this
The Sparkledammerung has a Twilight drinking game that's very simple. Take a drink every time you read the words "ghost/ed, "beauty/iful," "obsessed/ive," "chagrin," "ugh," "rainbow sparkles," "dazzle/ling," and "perfect/tion/ly. According to the word count, "perfect" and its variations has over a hundred uses in Breaking Dawn alone.
Proper maths indicate your Blood Alcohol Content will be 3% by this rule alone, reading only the first book (Assuming a 180 lb. social-drinking male who can read it in six hours). Just for comparison, the legal driving dose limit in the US is .08% BAC, and the lethal dose of alcohol is .4% BAC.
Take a shot every time another, greater piece of literature is mentioned and two shots for being placed in the wrong genre (Romeo and Juliet being treated as a story of true love... though obviously not as true as Bellaward), three if her facts are completely wrong/out of context (which makes a total of six for Romeo and Juliet alone: Mentioning, wrong genre, and for the lines being lines of true love).
Midnight Sun: Take a shot every time Edward uses the word "human". You'll be thoroughly wasted by the halfway point of chapter one.
For every time Bella talks about the weather, take two sips.
For every time someone murmurs, take a sip.
(For movies) Take a shot every time you see a guy without a shirt
Take two if he takes it off onscreen
Take three if it's a 'werewolf' and he has NO CHEST HAIR.
poped collars on shirts/jackets.
a youtube video had this as part of their shot check list, and let me tell you they were wasted halfway through because of that alone