Most good stories start with a fundamental list of ingredients: the initial situation, conflict, complication, climax, suspense, denouement, and conclusion. Great writers sometimes shake up the recipe and add some spice.
Initial Situation
Dorothea marries Mr. Casaubon; Lydgate marries Rosamond
Already, the plot of Middlemarch goes against traditional Victorian plots. Usually, the protagonist gets married at the very end, but here, these two couples are married by the end of the first volume. Dorothea longs to do great and noble work in the world, but she can't really explain what that work will entail. She thinks that marriage to a scholar like Mr. Casaubon will somehow satisfy all of her inexpressible longings. And Lydgate thinks that marriage to Rosamond will be like a chivalric romance. They're both wrong.
Conflict
Everyone is disillusioned by marriage
Dorothea discovers that Mr. Casaubon is too tied up in his own little world to pay any attention to her, and Mr. Casaubon begins to fear that Dorothea doesn't look up to him enough. Lydgate realizes that Rosamond's seeming docility is just an act and that she's really as stubborn as a mule, while Rosamond discovers that Lydgate lives for his work, and not for her.
Complication
Will Ladislaw shows up in Middlemarch
Dorothea is happy to see Will, but his appearance puts another strain on her marriage: Mr. Casaubon is jealous and suspicious of the friendship between Dorothea and Will, and he tries to stop them from seeing each other. Meanwhile, Will has made friends with Lydgate and Rosamond and hangs out at their house a lot. He's not conscious of it, but Rosamond is developing a crush on him.
Climax
Mr. Casaubon dies and leaves an unfair codicil in his will
The codicil in Mr. Casaubon's will makes it impossible for Dorothea and Will to see each other without causing a lot of gossip. The codicil says that if Dorothea remarries Will Ladislaw, she'll forfeit all the inheritance from Mr. Casaubon. The implication is that she wanted to marry Will in the first place. Will feels like he can't go anywhere near her without people whispering about how he's only after her money.
Suspense
Dorothea catches Rosamond and Will together
Dorothea is ready to ignore her dead husband's codicil because she has realized that she's in love with Will, but then she walks in on Rosamond and Will alone together. She thinks they're making out, but really Will is telling Rosamond to back off because he's in love with Dorothea. Will they ever get over this misunderstanding?
Denouement
Rosamond explains it all
Even after seeing Rosamond and Will together, Dorothea is generous enough to visit Rosamond to try to help her save her marriage. Rosamond is so touched by Dorothea's generosity that she tells Dorothea that everything was her fault – she was coming on to Will, and he was rejecting her, when Dorothea walked in. Will's in love with Dorothea after all!
Conclusion
Dorothea and Will marry and live happily ever after; Lydgate and Rosamond do not
The final chapter (the "Finale") explains what happens to all of the major characters. Dorothea and Will marry even though it means giving up Mr. Casaubon's fortune. And Lydgate and Rosamond live unhappily ever after. Until Lydgate dies and Rosamond is free to remarry.