The series started off as Two Guys, a Girl and a Pizza Place as two of the main characters, Michael "Berg" Bergen (Ryan Reynolds, Deadpool, Green Lantern, The Proposal) and Pete Dunville (Richard Ruccolo, Rita Rocks), worked in a pizza store near the college, and this part-time job location was a major set-piece in the series. While Berg and Pete were still in post-grad school, their best friend, Sharon (Traylor Howard, Monk), is out in the workforce in public relations for a major chemical company.
Each season of the series seems to introduce major changes. It's hard to tell if the format change was to refine the show's feel or an attempt to appeal to different target audiences. For instance, the First Season contained three major characters that are never referenced as soon as the Second Season begins. These include the pizza place's owner, Bill (Julius Carry, The Last Dragon), Pete's on-again/off-again girlfriend Melissa (Jennifer Westfeldt), and Mr. Bauer (David Ogden Stiers, M*A*S*H, The Dead Zone, Beauty and the Beast), a regular that gets his own life confused with various movies.
While the pizza place continues in Season Two, it looks more and more like Berg and Pete are running the business, even though Pete is applying to different architecture firms while Berg's medical school internship kicks into full swing. While Bill, Mr. Bauer, and Melissa are gone, the show does introduce two new characters in repairman Johnny (Nathan Fillion, Castle, Firefly) and fellow med student, Ashley (Suzanne Cryer). Sharon quickly falls for Johnny and it doesn't take long for them to start dating, while Berg and Ashley's relationship doesn't quite take flight so easily, especially given Ashley's sarcastic nature and the fact that she consistently beats Berg to the top-student position in all of their tests.
Season Three sees even more changes when the pizza place is abandoned and the show is renamed Two Guys and a Girl, even though the main cast has grown to include both Fillion and Cryer by this time. This season also introduces Irene (Jillian Bach, Julie & Julia) as an neighbor that obsesses over Pete. There are more changes as characters find different careers and some relationships grow stronger or break up, but going into more details would spoil many of the events that actually lead to some of the character growths over the series.
I remember watching this series off and on when it originally aired, but watching it all at once really helps to show how some of the actors grew across the four years. Chief among these is Reynolds. Early Two Guys, a Girl and a Pizza Place had Reynold's comedic style coming off in a very Jim Carrey manner, but he quickly refines his timing and style to what you would see in his more recent roles like Deadpool.
Two Guys and a Girl is a great example of a millennium-centric sit-com that focuses on 20-something's trying to get their lives started. It has a good bit of variety and provides enough forward momentum in the characters' lives that you never get the standard sit-com feeling that nothing ever changes. In fact, it kind of goes the opposite direction, given how drastically the show feels during its run.
While Two Guys and a Girl: The Complete Series isn't for everyone, there are plenty that will find it charming and fun.