How can I spread 500 unique business cards across 24 12x18" sheets?

First, if these are going out to commercial printing, you should hand the cards over to your printer and let them do this. Commercial printers generally have superior imposition software to do the job, and extensive experience at doing this day in, day out to get the most units per page impression. Plus, since you're paying the bill it's on them to make it right for you.

If you're doing this yourself, you're taking on a lot of responsibility to turn this job out right. Some factors to consider include:

1) How are the cards designed? Do they have bleeds off the 3½ x 2-inch final cut? On all edges? Or only some of them?

2) How are you going to print them? Consumer color inkjet printers have issues with sharp edge definition; color laser toner is very fragile and will look worse each time the card is handled.

3) How are you going to finish them? Hand cutting is perilous to your printed sheets and your personal well-being. Machine cutting could be a big problem too, depending on what you're using for your printing process.

But if you're going to do this act alone, I'd recommend two possible solutions for you:

Quite Imposing

and

Imposition Studio

Many smaller print shops use either one or the other solution with good results. They're not cheap, and the learning curve may cost you a fair amount of waste. Which is why I'd recommend you consider turning this project over to people who are already set up to do it.

Hope this helps,

Randy