If I understand the Akedat Yitshak (Parashat Metsora Sha'ar 67) correctly, he understands the Mishna to be saying that one shouldn't shun the minor mitzvot, since even the minor mitzvot carry inestimable reward:
אמר הוי זהיר במצוה קלה כבמצוה חמורה שאין אתה יודע מתן שכרן של מצות לעתיד לבא כו'. והכונה שיהיה שכר המצות בעיניו גדול הערך לאין תכלית עד כי בהזדמן לפניו המצוה היותר קלה שאיפשר, לא ידחה אותה לקטנותה אבל יזרז לעשותה כאלו באת לידו המצוה היותר חמורה שבתורה והטעם לפי שאין אתה יודע מתן שכרן של מצות וכו' ירצה שאין המחשבה מקפת בשום צד גודל שכרן של מצות עד שבקטנה שבכלן יש ויש שכר הרבה לפעולתך
He said that one should be careful with a minor mitsvah as with a major one, for you do not know the reward granted for mitsvot in the future etc. The intent is that the reward for the mitsvah should be perceived as great beyond measure, to the point that if the opportunity to perform even the most minor mitsvah presents itself, a person shouldn't shun it for its insignificance, but should zealous;y pursue it as though he had the opportunity to perform the most weighty mitsvah in the Torah. And the reason is that 'you do not know the reward granted for the mitsvot.' That is to say, that the mind simply cannot comprehend the magnitude of reward for mitsvot, such that for even the very smallest, there is great reward for your act.
Rambam, however, explains (in his commentary there) that the Mishna refers not to objectively small or large mitsvot, but to perceived small and large mitsvot:
שראוי להזהר במצוה שייחשב בה שהיא קלה, כגון שמחת הרגל ולמידת לשון קודש, ובמצוה שהתבארה חומרתה, כמו מילה וציצית ושחיטת פסח. ושם סיבת זה, שאין אתה יודע מתן שכרן, ובאור זה הענין ... מצוות עשה - לא נתבאר שכר כל אחת מהן מהו אצל ה', עד שנדע מה מהן יותר חשוב ומה מהן למטה מזה, אלא ציוה לעשות מעשה פלוני ופלוני, ולא ייודע שכר איזה משניהם יותר גדול אצל ה', ולפיכך ראוי להשתדל בכולן
That it is fitting to be careful with a mitsvah which he perceives as minor, such as celebrating on the festivals and teaching Hebrew, besides for a mitsvah whose importance is clear such as circumcision and tsitsit, and the korban Pesah. And he gave the following reason: that you do not know the reward granted for the mitsvot. And the explanation for this is...[that] positive commandment--the reward for each one has not been specified by God, to the point where we would know what is more important and what is considered less important to God. Therefore, it is appropriate to exert oneself for all of them.
It should be noted that even Rambam places different value on different positive mitsvot. (As he hinted to with the tsitsit example). For example, he writes (Hilkhot Mat'not Aniyim 10:1) that we must be more careful with charity than with any other mitsvah:
חייבין אנו להיזהר במצות צדקה, יתר מכל מצוות עשה
We must be more careful with the mitsvah of charity than with any other positive commandment.
In that case he demonstrates this with different verses about its importance.
In summary, according to the Akedah, one can know (he doesnt say how) that some mitsvot are more important than others, but should nevertheless madly pursue the lesser ones, for even their value is mind boggling. Rambam on the other hand concedes that you can know that importance of some mitsvot, such as tsitsit and charity, (based on scriptural evidence n the case of the latter and perhaps the former), but nevertheless focuses on the fact that in general with positive mitsvot we don't know which are which, and therefore should treat them equally.
