Hopefully others will have more specific advice, but since I just spent a while messing around with a Toshiba Gigabeat, I'll try.
Depends on the portable player. First, there are a couple of free projects that between them support a number of players:
Synctunes (pretty good):
http://www.nesfield.co.uk/synctunes/
XJNB (older):
http://www.wentnet.com/projects/xnjb/
iTuneMyWalkman (currently out of date, for reference):
http://ilari.scheinin.fidisk.fi/itunemywalkman/
...so one or more of those may handle any given player. There are also others, but those are the ones I've looked at recently.
If it's a player that acts as a mass storage device (and you don't mind using iTunes for your playlist app), you can "manually" manage your playlist as well, by just dragging and dropping what you want on the thing. The Gigabeat I mentioned, for example, worked this way, and since it only holds 1GB that ended up being easiest for the owner.
Some players might also have iTunes plugins or their own software that's Mac compatible, I suppose.
As a last ditch (though I can't say I'd recommend this under most circumstances) you could also run the player's Windows-only software via a virtualized Windows environment, but that's obviously kinda silly unless there's a very good reason for it.
All that said, the iPod of course works very smoothly on a Mac.
Just for reference, if you're wondering about non-iTunes/QuickTime media players ON the computer, there are many--VLC is the best known, but I have probably a half dozen installed right now.
