good question. the 3rd guard for sure helps. i did not expect it to be so, but what i found pursuing an elite press at all costs was that the turnover creation at the 3 remains highly important while i saw a major drop off for the 4 and 5. my experience was that pushing for crazy speed at the 1-3, and crazy good defense in general (def/spd/ath) from the 1-3, yielded great returns and was always worthwhile. however, adding additional guards or SFs at the 4 and even 5, i got basically nothing.
what is unclear to me though is the extent to which, for example, good turnover creation at the 4 can offset less than stellar players at the 1-3. for example, i never tried a really speed 4 with slow crappy sg and sf. my overall belief is that turnover creation is a team sport (this is almost certainly true) and that basically you hit diminishing returns at a certain point - put simply, the game won't just let you run 10 guards and create 30 turnovers a game. i think the contributions to the team turnover creation score, if you will, are heavily weighted with a small dropoff from 2 to 3 and a major drop off to the 4 and 5... where a high end 1-3 defensively / turnover wise essentially 'maxes' your score, but where the 4 and perhaps even a little bit the 5, could help with turnover creation in lieu of a strong 1-3 defensively. however because they are significantly smaller contributors, the 4/5, i'd expect to only chip away at any deficit in the 1-3.
to your point about the negatives, it is mostly the rebounding as you suggest it could be. i do think interior defense takes a hit, but interior defense is essentially def, ath, and blk, and a guard at the 3-4 will usually be an ath type guard not a speed type one (or at least a hybrid), and thus will probably be on par with the big or sf they are replacing, in ath/def terms, but of course that is a generalization. in press, blk matters the least of any scheme, so the relative hit from less blk in that guard is not that big, but if you are giving up ath/def, this is noticeable. i worked hard to try to use 4 guard lineups on super high end teams against really high end competition, and i couldn't make it work, but it was almost entirely due to the difficulty in replacing the rebounding, and that was usually with really good rebounding guards / sfs making the slide right, where i felt i was almost ideally suited for the slide (they also would have been really good ath/def wise).