How should I punctuate "Dave and Sarah, and Fred and Jane"?

I am assuming that the reason you aren't putting a comma between the first three names is because you want to indicate that Dave and Sarah are a couple and Fred and Jane are a couple.

The following would be inappropriate for this purpose:

Dave, Sarah, Fred, and Jane were two of the three-legged race teams.

Unfortunately, we can't use parentheses to express what you want:

(Dave and Sarah) and (Fred and Jane) were two of the three-legged race teams.

Your own representation serves the same kind of purpose as the parentheses, but it's also not how punctuation is meant to work:

Dave and Sarah, and Fred and Jane were two of the three-legged race teams.

A nonstandard way of punctuating this, but one that could be considered acceptable, is to use a semicolon rather than a comma:

Dave and Sarah; and Fred and Jane were two of the three-legged race teams.

Although I've personally never thought a semicolon seemed appropriate with only two compound list items, and I would always choose to rephrase such a sentence altogether, it's an option.

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The following is syntactically correct—but extremely difficult to parse:

The couple of Dave and Sarah and the couple of Fred and Jane were two of the three-legged-race teams.

This is slightly better but still strange:

Team Dave and Sarah and team Fred and Jane were two of the three-legged race entrants.

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I think the only way of making this work is to rephrase the sentence.

Possibly one of the following two sentences is correct—but they are both awkward because of the subject-verb agreement:

Dave and Sarah was one of the three-legged race teams; so was Fred and Jane.
Dave and Sarah were one of the three-legged race teams; so were Fred and Jane.

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In short, I think this might end up being the only way of expressing it in a way that isn't awkward:

✔ Dave and Sarah formed one of the three-legged race teams; so did Fred and Jane.

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Finally, note that this becomes simple if there are at least three couples:

Dave and Sarah, Fred and Jane, and Jim and Molly were three of three-legged race teams.

Since the type of sentence you're asking about is commonly used in speech nowadays, the rules of punctuation should be made to adapt to it (because grammar arose from how we speak, and therefore must continue to evolve.)

Thus, "Dave and Sarah, and Fred and Jane" is correct, with the comma functioning as a tiny pause in uttering the sentence (read it in your head and pause a little when you arrive the comma).

If you intend to use this in a formal piece, however, I suggest rephrasing the sentence.

Hope this helps.