Thanks all. My onward flight from FRA is to CPT, and there's only one flight a day, so that pretty much makes my decision. I'd still like to get a little more color on domestic-to-international transfers at IST, though.

What I am actually trying to do is get myself from ESB (Ankara) to CPT on a Friday. TK's red-eye from IST-JNB doesn't run on Fridays, so I am left with basically two options: ESB-IST-CDG-JNB-CPT using TK/AF/SA, or ESB-IST-FRA-CPT using TK/LH. There is also EK via DXB, but the connection is awful, three hours at DXB between 1 and 4 AM. No thanks.

The ESB-IST-FRA-CPT version seems the least objectionable, but it would require one of those two tight connections, given my time constraints (I can't leave ESB until 4 PM). The ESB-IST-CDG-JNB-CPT looks safe on the connections, but just that much more nightmarish with four flights in a row, instead of three.