We report the enhancement of the fluorescence emitted from dye-labeled DNA upon co-aggregation with silver nanoparticles. The co-aggregation process is induced by the polycationic molecule spermine, which both neutralizes the charge of the DNA backbone and aggregates the nanoparticles. This simple method generates nanoparticle aggregates with very short (1–2 nm) inter-particle distance. Even though no spacer layer was used, large enhancements of the fluorescence, in the range of 15–740× (depending on the original quantum yield of the dye used), were observed. Theoretical modeling shows that this occurs as the local enhancement of the electromagnetic field near the hotspots is sufficiently large to overcome the quenching by the surface, even at short distances of 1 nm. The predicted trend of increased SEF enhancement with a decrease in initial quantum yield is observed. The average enhancements observed in this system are on-par with the best results obtained on nanostructured surfaces to date.