i think it would be terrible in d2/d3 where the individual minutes are so important!!
i ran zone OR press in d1 tark for a while at kansas, which probably isn't the ideal place to employ such a set (i'd rather be somewhere really crowded like the east coast, for that setup). we had a good run for a while, 5 season stint with 2 runner ups and 2 titles, one with zone, one with press. it definitely can work, but im moving away from it. it was really a for-fun experiment more than something i thought had a chance of being the optimal setup - the problem is, you are always a little behind on your IQ, so your best teams are never quite as good as your best teams should be. it does level things out on the bottom end though, those low rosters with press can be pretty brutal.
when i did it, i used 57m of team practice - 20 in motion, and 20/17 in my defenses, depending which i needed. then i started cheating, the title shot years i'd be like 22, maybe 24 in press, when it was a press year, and that started to catch up with me a bit later. i was trying to learn zone on a few teams at once, thats part of why i did it, and im not really a huge fan now after all that (for title shots only, its a fine set for everything else). so im moving away but it was a fun little challenge. it only could work though because i was able to mostly sign guys who were already game ready, rating wise, when they walked in the door. if you aren't an a/a+ BCS school it seems like those practice minutes would really cost you - and they did for me, with certain players - the higher potential guys who i could sign other places, just never really panned out for me, or didn't until senior year, which is totally not worth it.
so all in all, can you do it? sure. can you be really successful? sure. is it optimal, purely from a championship winning standpoint? i doubt it. but not by that much. i doubt i would have won the zone title i won if i only had press, although the two years i got runner up with press, maybe if i had better press iq, we would have won one? and the press title was the first elite team i had in 5 years, maybe, it was a borderline case (my definition is a little ridiculous there, truly elite = 50% to win the championship). so its not like i really felt the multiple defenses dragging me down in a big way, but also, every time you sit there with a championship contender and its hmm i wish i had that extra partial grade in IQ across the board... it kind of makes you wonder. and also, theres just that extra learning curve, you have to adapt how you play in a number of areas, to compensate for the new system. if i wasn't pretty engaged at the time i took it on, i probably would have been awful at it. ultimately i did it for fun and for those reasons its great, and you can have a lot of success with it. if you are just chasing championships, i think its a little too much to juggle to really be considered an ideal approach. although if your recruiting is shaky, it might be more valuable - now that i know kansas and can anticipate my neighbors, and am a pretty good recruiter, i can even things out on my own, well enough. but early in my recruiting days, the option to run zone when i screwed up royally in recruiting, that would have been much, much more valuable to me.