It's undeniable that bigger and stronger people always have the first initial advantage when fighting. The "size does not matter" phrase, is more of an ideal, an ultimate goal of every martial art, rather than how it really is. That's why they have different weight divisions in almost every type of fighting sport.
Overcoming the size, reach, power, and the weight of the opponent with only skill.. I'd say that's pretty much impossible, even for trained fighters in professional bouts. I mean, there's a reason why school bullies have thrived through thousands of years of human history
..
However, martial arts can provide an intimate knowledge of various situations concerning combat. Where to hit, how to hit, and etc etc.
In that sense, like Naso says, Judo, Ju-jitsu and Aikido is probably some of the best martial arts to learn for self-defensive purposes. Because, usually not even the strongest people can withstand a stretch, lock, or a twist on the joints.
Granted, that stronger and bigger people with more strength can resist better, but that's usually with trained fighters.
Most ordinary people don't have much knowledge in what their joints can do, or how they may be attacked. They instinctively avoid one part of their joints being stretched or locked, but when a move comes that attacks all sorts of joints at the same time systematically they usually cannot resist that.
The fact that Judo and Jujitsu became such a powerful martial art even in professional fights, is that the opponents are matched at zero-distance. At this one time, I met a friend of mine who practices jujitsu. We were both drunk, and with a spot of fun, I urged him to show me some of the moves he practices in a nearby park.
Now, I'm 6 ft. 4" and weigh about 220lbs, used to bodybuild a bit(all flabby now, tho' lol
), and my friend was at least 5 inches shorter than me and much lighter.
We grabbed each other by the waist, and in a flash, he tripped me down. And then geez, he was climbing all over my body like a cockroach, and before I knew what happened, he locked my arm in a classic arm-bar before I could even try to resist by tensing arm muscles.
If it's a 1vs1 situations, the chances are, if you really have to seriously fight, a combination of jujitsu, judo and aikido will be the most efficient in totalling the guy