When I was first C-Dory shopping, I wanted a boat with twins. Not for any "real" reason, but just because I like the symmetry and think they look cool. Of course, that's all the reason one needs!
However, every boat I could find with twins was "wrong" in some other way (poor condition, color I don't like, high top when I wanted low top, etc.) The pristine ones that had all the other features I wanted all had single/kicker setups. I found one that was so just right (for me) that I decided to buy it, and immediately mentally dedicated the "extra" money for a re-power to twins.
I never found any stoppers if that's what I decided to do. Here are some of the considerations I found:
1) On some of the boats with twins, they moved the splashwell drain to the center (otherwise apparently one of the twin brackets covered it). If that was done on your boat, you'd want to re-establish the usual drain. You can tell where the "normal" one is because the splashwell molding has a sort of trough there (it's starboard of center).
2) As you mentioned, the engine mount holes would need to be closed and new ones made. To me, this isn't much of a negative, because I re-did mine anyway due to lack of the core being protected. This would be a great chance to fill the twin holes solidly and protect the core on the new holes.
3) You'd perhaps be removing one "control" at the helm (depending on how deluxe your kicker is); and likely you'd be going with a different/newer one. This might give you more room next to the helm seat.
4) You'll have an extra gauge hole at the helm, but they make various things that fit that size hole (even little stereos); or you can make a "cover plate" for the whole helm gauge area and then just cut holes where you want them (thin wood, starboard, other plastic, etc.). If you go Yamaha again, they have a second (same size) gauge you can get that shows more things (unless you already have that setup and thus have four gauge holes...).
5) You'll likely gain some space by removing a battery (presuming you have two start batteries?) and perhaps a fuel filter (I ran original kicker off same filter/tanks as main, with a quick release fitting so it could also go right to auxiliary tank).
6) You'll want to consider which side to put the kicker on. Each side seems to have plusses and minuses. Mine came to starboard, which I prefer. The good is that then the/a swim platform is to port, and you don't have to clamber over all the rigging wires/fuel lines. Also the tiller handle (if you have one) is clear of the splashwell side). On the other hand, it's more weight to starboard, which may be an issue if you don't have a passenger, have a lot of weight to starboard, etc. If the kicker is on port it's the opposite set of pros/cons.
As for me, after a season or two with the single main/kicker, I decided not to change to twins. I still think they look much better (lower, more symmetrical, don't come forward as far when tilted, and just cool), but found things I preferred with the setup I have that I don't want to give up. So now if/when I re-power, it will most likely be to a single again. Here were my "discoveries":
1) I found that I use the swim platform (and the open area of the splashwell leading to it) ALL the time on places like Powell. When beaching (I like to anchor the bow out and go in stern-to), when setting a stern anchor (I do it from the swim platform plus a small "bridge" platform I made that goes across the splashwell). Also (not beaching-specific) it's where I board the dinghy/kayak. You can fit a small swim platform with twins, but I now wouldn't want to give up the "big" one that I have with the single/kicker.
2) Although there are "problem" situations that favor either setup (and who knows which one you will encounter), I found that I feel comfortable with one engine (and its prop) up and out of the water, especially when I'm running on plane. I would have to take the time to lower it, and then I don't have mine set up for remote steering and throttle as a twin would be, but to my mind neither way is perfect, so it's just a matter of choosing.
3) I spent some time on similar boats with twins, and although maybe it's just me, I found that I "had" to have them perfectly synchronized or it would drive me nuts (I could hear a slight "hunting" otherwise). So I was often fiddling with the controls. I think it might be distracting for me in the long run (although I never did spend more than a couple of hours out cruising on a boat with twins). This may not be noticeable to others.
4) Side bonus, but it would be less expensive to re-power with a single vs. twins (but I'd pay the extra anyway if that's what I really wanted; however, see above reasons).
I don't fish (yet?) so those considerations weren't on my mind. I still think twins are cooler though, and they definitely also have plusses. I was just listing above why I ended up liking my single.
PS: Has someone gone to Hardee's house to check on him yet? Maybe bring some smelling salts...
