1) One of the explanations of "Ein Isur Chal Al Isur" is that the Torah does not forbid something which is already forbidden. The Torah only comes to prohibit things which were previously permitted. For instance, if someone eats Chazir together with milk, he does not transgess the prohibition of meat and milk, because the meat was already forbidden since it is Chazir. Since it was already forbidden, milk and meat will not add an extra Isur to the act, because "Ein Isur Chal Al Isur."

2) According to this definition, our Mishnah would not fall into the category of "Ein Isur Chal Al Isur." If he plows with an ox and donkey, this Isur has no connection with the different Isur involved because the latter are holy. It is not similar to the Chazir cooked with milk, because it is the same meat which we would want to receive an additional prohibition, namely Chazir meat cooked with milk. In contrast, there is no connection between the Isur of ox and donkey and the quite separate fact that they are Mukdashin. Therefore, there could be two sets of Malkus -- one for ox and donkey, and a separate set for Mukdashin -- because they are two totally different Isurim.

3) The Mishnah on 21b is different from the Mishnah at the top of 4b. There, the question is whether he both pays and receives Malkus. The Rabanan maintain that we do give someone both a financial punishment and a physical punishment. In contrast, the Mishnah on 21b involves more than one physical punishment, and the Rabanan can agree that we may give two doses of the same kind of physical punishment.

4) After taking more time to look into this important topic, I came up with what I hope will be a better answer to your question:

The Rambam that you cited writes that "Ein Isur Chal Al Isur" does not apply in our Mishnah because "they are many Isurim all doubled up at one time and therefore it is not impossible that many negative commandments could join together simultaneously."

What the Rambam writes fits with an idea that I wrote earlier. This is the idea that "Ein Isur Chal Al Isur" means that the Torah does not prohibit things which are already prohibited. It follows, according to this, that if the Isurim all suddenly apply simultaneously, it is possible that several prohbitions can all apply together, because none of them applied first before all the others applied.

5) The Achronim do ask some questions on this rule of the Rambam. The Sha'agas Aryeh (#60, DH M'M) asks about the plowing in the Sabbatical year and on Yom Tov. The Shemitah year starts right at the beginning of the year, while Yom Tov could be at any time during the year, so how can the Rambam say that the Isur of plowing in the seventh year and the Isur of plowing on Yom Tov start simultaneously?

6) The Sha'agas Aryeh answers that when the Mishnah refers to plowing on Yom Tov, this means specifically on the Yom Tov of Rosh Hashanah. Accordingly, the Shemitah year, and Yom Tov of Rosh Hashanah, start at exactly the same time, so these two prohibitions can take effect together.

7) The Sha'agas Aryeh proves that Rosh Hashanah is considered as a Yom Tov from the Mishnah in Rosh Hashanah 29b which states "Yom Tov of Rosh Hashanah." This proves that Rosh Hashanah is considered a Yom Tov, in addition to being the Day of Judgement.

8) I do not wish to go off on a tangent, but it is interesting to note that I have found two other places in the Sha'agas Aryeh where he discusses whether Rosh Hashanah is a Yom Tov. In #67, he writes that while Yom Kippur and Rosh Hashanah are considered "Mo'ed" for certain matters, there is not an obligation nowadays for a person to purify himself by going to the Mikveh before Rosh Hashanah. However, in the #102, the Sha'agas Aryeh writes that Rosh Hashanah is considered a Yom Tov in that there is a Mitzvah of being happy on Yom Tov, Simchas Yom Tov, on Rosh Hashanah. The Sha'agas Aryeh cites proof from the Mishnah in Rosh Hashanah 29b that he also cites in #60, as I mentioned above.

9) There is a practical ramification for the above question. I once asked Rav Chaim Pinchas Sheinberg zt'l, the Rosh Yeshiva of Torah Or, if there is a Mitzvah to drink a Revi'is of wine on Rosh Hashanah. He replied that it is good to drink a Revi'is of wine, because the Mishnah in Rosh Hashanah 29b calls Rosh Hashanah a Yom Tov. However, when I posed the same question to Rav Yosef Shalom Elyashiv zt'l, he replied that one is not obligated to drink a Revi'is of wine on Rosh Hashanah. Rav Elyashiv said (translated): "We do not take on like the Sha'gas Aryeh."

Kol Tuv,

Dovid Bloom