it is possible (with difficulty) to design a frameset that will take wide-ish road tyres and still allows you to use a 'road' chainset and chainline. But most such OTP framesets that accept wide tyres have chainstays that are positioned so that they will interfere with a classic 'road' chainset. The clearance on any given frameset is affected by both the chainline and the chainring size.
I have found that if you talk much about the benefits of a good chainline in the most used gears these days you are liable to dismissed as an old fart; it doesn't play well with the 'chains as thin as spaghetti at any angle' and '1x' ethos that prevails amongst the more, uh, 'fashion conscious'. But if you have the slightest concern with real efficiency you should give it more mind than most folk do.
If you do the sums it turns out that, for most riders, to make the transmission 0.5% more efficient even if it means the bike is about 0.5kg heavier is still a 'win' even if you are climbing most road grade hills; the gradient needs to be very steep indeed before it the extra weight is a significant detriment.
Easily avoidable losses in derailleur transmissions stem from three main sources
1) pulleys (you can save 1-2W in some cases)
2) chordal losses
3) cross-chaining losses
Chordal losses arise whenever the chain links have to articulate more than they might otherwise. Using a smaller chain pitch reduces chordal losses (at any given speocket diameter) but this isn't a practical option; you are stuck with 1/2" pitch chain. The practical option is simply to run as large chainrings and sprockets as possible for any given gear ratio. Thus running 30/15 gives the same gear ratio as 50/25 but (at the same chainline) the latter is liable to be 1-2% more efficient.
Cross-chaining losses are of comparable magnitude. Thus if you have a choice of a small-small combination with a good chainline, and a big-big combination with the same gear ratio but a bad chainline, quite often the efficiency is about the same.
The trick is to ensure that the gears you use most have the best combinations of chainline and sprocket size. In practice this means, (on the road riding endurance events) that there are two regimes that are worth concentrating on;
a) flat roads and
b) graded climbs
By graded climbs I mean those found on well-built roads; these are usually between 5 and 7% in most parts of europe and only become steeper than this if it is unavoidable or the route is unlikely ever to be/have been used by heavy vehicles of any kind. If you analyse your riding you will most likely find that you spend about three quarters of the time on the bike using those kinds of gears.
This will vary from rider to rider but it might boil down to (say) having a gear of about 70" for the flat and another about 30" for the climbs If you choose well you can make these gears ~1% more efficient and as a bonus the transmission parts may last longer too. In most cases I would choose to not have a very high top gear ratio if this gave me better efficiency on average; for example (except in massed start racing) an 11T sprocket is basically a waste of time in my book; it is inherently lossy in use, you might only use that gear ratio when going downhill (when you might be better off saving energy) and it being there pushes all the other sprockets to the left, buggering up the chainline quite unnecessarily.
For example some years ago I built a bike that was basically road bike with a 'bail out' third chainring, so a 13-28T cassette and a 30-42-52 chainset. This (because of the parts chosen) gave a good chainline on 52/19 and 52/17 for the flat and also a pretty good chainline on 30/24 and 30/28 for the steep climbs. And of course plenty inbetween. The bike didn't have to accept fat tyres so I was able to make the chainline on the middle ring not much different to the inner ring on a road double; this wasn't without consequence; I almost tore my hair out getting a FD to work OK on the small chainring. But the net effect was that the bike's gearing suited me very well and under most conditions I wasn't forced to use a lossy gear.
cheers
