The first rule of knife fighting is RUN AWAY!!! That important aside, your question is about what to have on you when you can't run away. If you were in a situation where you would require a weapon to get out of it, then you are at the second rule of knife fighting. That rule is simply, if you are going to knife fight, have a knife.
So, don't give up on folders if you won't carry a fixed blade. If you have no problem carrying a fixed blade, sell your folders then.
Personally, I rarely carry a fixed blade. I may have one in a bag with me on occasion, and sometimes for a while when I venture out of my house I will have a small fixed blade on me (those 4" fixed blades, as Steve pointed out, are great.) Otherwise, most of the time if I have a knife on me it will be a folder. I won't give up on folders just yet. If I did, I'd be rendering myself defenseless.
Now, remember that I said this assumes you are in a position where you NEED a knife. I have 7+ years of MA training under my belt. I am confident that when I pass by the typical drunk that I may encounter in the rough part of down town, I can run away just fine. If I have to fight, I have the empty hand skills to do what needs to be done. but I am smart enough to realize that I may not be able to take on packs of sumbass teenagers that tend to roam around on occasion. I know that sometimes these punks have weapons on themselves as well. So, I have my utility knife with me that would be pressed into self defense duty.
Also, the argument was made that one should just avoid places and persons where you may need to use a knife in self defense! THat is great advice, but not a good enough argument for you not to carry for self defense. One day I was lounging in a chair at home watching t.v. and playing with my Cold Steel LTC kukri. By playing I mean just holding it, appreciating the knife. In burst a woman crying and very wooried, asking me to protect her. A few second later popped in her abusive boyfriend. In that case, the crappy situation found me. i'd like to think that the kukri in my right hand was part of the reason that the bad guy left. I did stop the guy inside at my door, told him firmly to leave and I pushed him towards the door with my free hand. But thanks to me having a knife on me, I had backup just in case.
Now, about knives themselves. You have to realize that these are mechanical things with strengths and weaknesses. If I am in a situation where I need a knife to get out of it, I'd rather have a slip joint folder on me than nothign at all! As Phil said, you have to learn how to use your gear properly. Find a folder with a generous finger cut out. Something like a benchmade AFCK handle is awesome for that. If the sscales on your folder are smooth, get out some sand paper and roughen them up a bit. Or send the knife to a maker who is willing for some bucks to sandblast your scales. Get a knife that is build around the lock. Folders like the TOPS CQT series are supposed to be real tough. E-mail Brian Jones and ask him about these folders. the Buck Strider is supposed to be big and beefy as well. CRKT makes folders liek the Kasper series with the LAWKS system. LAWKS is just a gizmo that interferes with the liner so that the liner can't close without you manipulating the LAWKS safety.
Again, let me reiterate my main points and tie it all together. If you are in a situation where you NEED a knife to get out of it, you will NEED to have a knife on you. If you can't or won't go fixed, folding is your only option. A lsip joint in these situation sis better than no folder. Get a folder that is designed for retention (AFCK, CRKT kasper designs, etc.) There are some great locks out there, learn about them. Don't be afraid to tweak your defensive folder. Sand those smooth scales so that they are grippy. If you are wanting the best self defense folder, save up for a custom. And whatever you carry, if you carry with self defense in mind at all you'd better train with it. Even draw and opening drills will make you more useful in a self defense situation.
Here's one drill for you. Stand infront of the t.v. with your folder in your usual carry position. Everytime a particular character on a show appears, draw, open and slash. Replace your knife. Repeat.
God luck.