Middleton College is a small, liberal arts college in Lawndale where Jake Morgendorffer and Helen Barksdale met and began dating during the late 1960s. They graduated in the Class of '72 ("The Daria Database"). The campus is revisited in "College Bored," and is referred to a few times through the series. Coyote Yeager and Willow Yeager were presumably at Middleton as well, as the four knew each other in 1969 and would go on to live in a commune together after graduating. ("That Was Then, This Is Dumb")
"Mad Dog" Morgendorffer paid for Jake to go there, when Jake would've likely been drafted for the Vietnam War otherwise - or, worse, dropped out to become a hippie. ("The Daria Diaries") Mad Dog may have thought Middleton, due to its religious background, would stop Jake dropping out (oops).
What we actually know about Middleton is limited. It has a long history, going back to Colonial times, when it was a religious all-male school. ("College Bored") It is considered to be a second-tier school (near the end of the series, we learn that they have "gotten rid of all the requirements, so you can take whatever you want!!"). It has such a reputation that Grove Hills uses Middleton as an example of the type of place your children might end up if you don't send them to Grove Hills. The alumni newsletter is Middleton Musings.
Helen only attended it because it was the height of the baby boom, and getting into a better school was hard. Jake, however, has described it as a family tradition, though we don't know if he means other Morgendorffers went there or if he just means him & Helen. He does like to think it's a brilliant college, which his wife chalks up to his need to delude himself about parts of his past in order to function. (Is It College Yet?)
Helen keeps missing class reunions and swears she'll make the next one, though she did invite some fellow alumni to her twenty-third wedding anniversary party - aside from that, she doesn't seem to keep in contact with her old classmates, as she managed to lie to them that Daria "had the flu, which sapped her energy" and is normally cheerful. ("The Daria Database")
Other students from the Class of '72 are shown in "Database's" copy of Middleton Musings to be a bit rubbish: "L.A. transplant" Marjorie Kurtis is noted to have "given up her acting/food management careers" to become a self-published author (The Art of Acting is her first), Doug Preston is working behind the counter at the Turquoise and Trinkets store in Santa Fe, Nancy "Woodsy" Woods has passed the bar almost twenty years after graduating Middleton Law in 1979, Lad Duncan is a snowboarding instructor.
When Daria and her family visited the college, the current Bursaw was a corrupt, dodgy man: he refers parents who need loans to a "family business" who have "very agreeable terms" and have "a variety of interests"...
Middleton College in Fanfiction
Jake and Helen's days in college have been covered in several fanfiction stories or series, including "All My Children", "The Lost Seasons" and "Falling Into College". In the John Lane Series, the football team is called "The Mud Daubers".