Spoiler alert!
Proceed with caution.

Obviously, there are many differences between the movie and the graphic novels. I've read through the comics twice and seen the movie about three times, so I know I haven't caught them all, because Bryan Lee O'Malley (a.k.a. Kupek to all you fans of his music) is just a genius like that, but here is a place to point out and discuss the differences.

Lisa

First of all, Lisa. Lisa has a cameo in the movie, if nobody has noticed. She is mentioned by Julie. This isn't in the memorable quotes on imbd.com so I may get Scott's exact words wrong, but you get the gist of what he's saying. (Anybody that owns the movie, as I sadly don't, can feel free to PM me and I'll edit it and put a little thank you note crediting you for correcting me.)
This is at the part near the beginning at which Scott meets Ramona.
Bryan Lee O'Malley
Julie: "Everyone knows you're a ladykiller wannabe jerky jerk."
Scott: "That is so not true!"
Julie: "That time with Lisa?"
Scott: "It was nothing."
Julie: "That time with Hollie?"
Scott: "Nothing happened."
Julie: "That time with Kim?"
Scott: "Oh, come on, Kim? We're totally cool now."
[Scott turns to see Kim glaring at him from across the room.]
This is a relatively quick line, so it took me until my second time through to catch, but... Julie doesn't know Lisa. In the comics, Scott moved to Ontario when he was in high school and met Lisa on the first day of school while sitting outside of the principal's office after getting into a fight. Later that day, he met Kim because they were partners in their social studies class. (Anybody know what the name of the class was?) Lisa wanted to form a band before long under the logic that she wasn't a goth and Scott wasn't a jock so they needed to fit in somehow, and, though Scott initially disagreed, they ended up forming the band Sonic & Knuckles, but needed a drummer. After seeing Kim playing drums for the school's band department, Scott said he knew the girl and Lisa said she'd get her some eyeliner. Kim agreed to be their drummer when Scott asked after saving her from Simon Lee, at which time he also asked her out. They dated until Scott moved to Toronto, where Scott met Stephen Stills, Julie, Envy, etc., and went to college with all of them. Kim followed soon after, later forming Sex Bob-Omb with Scott and Stephen Stills. Lisa did not come to Toronto until volume 4, which was the first meeting between her and Julie.

Scott's Origins

In the comics, as mentioned above, Scott moved to Ontario and went to high school there, then moved to Toronto. In the movie, Scott shows Knives 'the house he grew up in', which is across the street from his apartment with Wallace, immediately before his first dream involving Ramona.
Notice, in the movie, that, at the beginning, Kim asks Scott how long he's been out of high school even though, later on, she tells Ramona that they dated in high school.
(Could someone verify these quotes for me?)
Bryan Lee O'Malley
Kim: "How long have you been out of high school now, Scott, like 13 years?"
Scott: "I'm not playing your little games."
Kim: "So you're like 28?"
Scott: "I'm 22."
Box: [Scott Pilgrim, Age: 22, Rating: Awesome]
*Also note that he is 22 in the movie, but 23 in books 1-4 and 24 from volume 5 forward.
Bryan Lee O'Malley
Kim: "I actually dated Scott in High School."
Ramona: "Oh? Got any embarrassing stories?"
Kim: "Haha. Yeah, he's an idiot."


Others

-Kyle and Ken Katayanagi have no dialog in the movie
-Gideon (Ramona's cat) has a cameo in the movie, even though he plays such a major role as the last remaining piece of Ramona when she goes missing in the comics--the cameo is the design on Scott's mug in the opening scene (which Michael Cera (who is the actor portraying Scott in the movie) is holding in a different position after nearly every camera angle change, if nobody else noticed)

Note: I know another huge one is Gideon Gordon Graves, who has, in the comics, 'The Flow' as well as his own seven evil exes. However, I can't remember many of the differences as there are so many, so anybody else can do it if they desire.