So what kind of performance drop do you see when you disable S3TC? On a 32MB card, the performance hit can be up to 50% depending on the situation (Quaver is the perfect benchmark for this); 64MB owners will be happy to know that they can disable S3TC without losing much performance because of all of the extra memory.
Is it worth it? It's not as noticeable as it would be if the walls or floors looked really bad, but for some gamers it is a big problem, so you can try experimenting with turning r_ext_compress_textures off to see if the game is still playable by your standards.