Strive for balance. Try to create a seating arrangement where no one feels like a fifth wheel.
I once had to fill two tables of ten at a charity benefit. Less than half of the guests were bringing a spouse or date, so I tried to work it out with 2 couples and 6 singles, 3 maile and 3 female at each table. Even if the singles don't know each other its good to have an equal mix of male/female if there is dancing at the party. But you have to be careful that no one feels as if its a set up.
Depends what the seating plan is for, But for a wedding, I got a large piece of paper, draw the tables out and write in pencil roughly where each guest goes. Usually I try and mix guests but at the wedding, grandparents, and parents sit near the top table, cousins and aunts and uncles next tables down, then friends and people you dont really know. Usually goes in importance. Eventually we just bought a huge rectangle, or made the tables into a big circle so no one felt they were stuffed into a corner.