Could someone clearly and succinctly present an argument against having slavery in a setting in such a way that their argument isn't an appeal to emotion? Because I really don't see the issue. Yes, slavery is bad. But I have no problem with it being in a setting, or for that matter the players owning slaves or enslaving people, or the PCs potentially being enslaved. If you care about simulating a plausible world, these are things that very well could happen. It would likely occur for much the same reasons it occurs in the real world, and would thus be thought provoking (at least, I certainly hope it would!). I also think people are focusing far too much on the transatlantic slave trade and completely ignoring other instances of slavery that have existed, in particular the ancient world and the Islamic world (as an aside, it was fairly common practice in Muslim empires to castrate male slaves (I believe this also occurred in China, and too a lesser extent Rome)). Excising slavery from a setting purely on the basis that it is bad, and claiming that it is a lazy/cheap tool to use when building a world is dismissive of people in the real world that managed to achieve remarkable things despite having been enslaved.
Someone earlier in this thread said you could remove slavery from your Fantasy Rome and it would be the same. No. It wouldn't. It completely changes things. Many things in Rome's history stem directly from it having had at various points in it's history, more slaves than free people. I also saw someone say (back when people were talking about Yasuke) that there was no reason you couldn't have Africans living in your Fantasy Japan. This is at best misguided, and at worst obtuse. Firstly, having Africans living in Fantasy Japan in large numbers makes light the achievements of Yasuke, by making him no longer so unusual, and secondly it makes your world highly implausible. Do you realize how geographically separated Japan and Africa are? The chances of relatively large numbers of Africans managing to get to Japan are slim at best.
Finally, I seem to remember seeing earlier in this thread someone comparing serfdom and slavery, and saying there was little difference between the two. This is far from accurate. Allow me to explain;
Generally there have been two types of slaves, "field" slaves and "house" slaves. Field slaves worked outdoors and were relatively cheap and expendable. House slaves were generally well treated and trusted, as they were specialists, often having been philosophers, skilled fighters, exceptionally attractive or well educated prior to their being enslaved. House slaves were often trusted advisors, messengers and confidants, at some times in some places slaves were even allowed to own their own property or manager their owner's property. Indeed, at some times in some places, people may well have been better off as a slave than if they were free, simply because it allowed them greater opportunities and freedoms than they would otherwise have had.
Slaves were also granted certain legal protections in various parts of the world at various times. Usually even a slave's owner wasn't allowed to kill them out of hand. It was also generally possible (at least in theory) for slaves to buy their freedom.
Serfdom is a bit more tricky to explain. This is because serfdom was never any single thing, and varied significantly by time period and region. The relationship between tenant farms and lords is highly contractual and based on mutual obligation, and is not standardized, meaning that you could have one farmer that is obligated to provide his lord with a share of each year's crops, and a second farmer with the same lord who instead is obligated to work the lord's land for a certain number of days every year or season. Tenants were usually expected to go to war on behalf of their lord for a certain number of days per year (the number of days gradual increased later in the medieval period as farming methods gradually improved and the demand for professional soldiers* increased).
Now we can get to defining what a serf is. A serf is generally a tenant farmer that has a hereditary right to farm a particular piece of land in exchange for a specific set of obligations between the serf and the lord that owns the land, regardless of who the lord is that owns the land. A serf may pay their lord a (variable) amount of money in order to become a "freeman" (i.e. someone not tied to a piece of land), this money is not to buy the serf's freedom, but instead to compensate the lord for the lost labour, and so the amount of money required could be influenced by the season and the value of the land**, among other factors.
A "freeman" works for money, something that has been greatly looked down upon for most of history in most places, and pays a lord in return for being allowed to work a particular piece of land.
*To clarify what is meant by "professional soldiers" I am referring mostly to the rise of mercenary companies, as knights are warriors, a warrior being distinct from a soldier in that being a warrior means being part of a specific social class (the "pyramid" model of social class is ill suited to the pre-early modern world) that is entirely built around warfare, whereas a soldier is someone that is enlisted (through whatever means) or obligated to fight in a conflict and then go home.
**Keep in mind that the land is not usually being bought by the now former serf and remains in the lord's possession.
To conclude, these definitions for serfs and "freemen" are not absolute. There are instances of people called serfs that had to pay their lord with money, and "freemen" that had obligations to a lord instead of paying them. Additionally, I am not a professional historian, only an enthusiast and the summaries of how slavery and serfdom worked for much of history are by necessity a broad overview due the variation across geography and time.
TL;DR: The transatlantic slave trade was unusually horrific and well publicized as far as slavery goes. There have been roughly two types of slaves in history: "field" slaves and "house" slaves, with house slaves being relatively well treated and often trusted, slaves were generally protected by laws, and could general (in theory) buy their freedom, and some people had access to opportunities and freedoms that they may never have had if they weren't enslaved***. Serfs are not in any way similar to slaves.
***To be absolutely clear that does not mean I condone slavery in any way. Only that there have been instances of slaves achieving remarkable things as a consequence of their contact with people they would otherwise have never met, and their own intelligence and skill.