Short answer: time signatures as a concept have limited utility in relation to music with coincident rhythms.
I believe that one of the under-appreciated aspects of blues is exactly the quality to which your question is addressed: the simultaneity of different rhythmic "feels," usually triplicate vs. duple.
I believe it derives from the polyrhythms in African music. Polyrhytms, which are common in the music of sub-Saharan Africa, are generally absent from occidental music prior to the integration of African and African American music with its forms.
Check out this music recorded in Ghana, often cited as an example of the African genealogy of blues:
The scratchy rhythm is what drummers would call a boogie shuffle. The melody is actually the straight rhythm
To my ears, the mojo mostly went out of the blues in the 1960s because rock players began to hammer out the shuffle beat in a ham-fisted way that does not allow for the transcendent feeling that occurs when players with a subtle touch slide around on the beat.
Here, for example, is a Howlin' Wolf song with a nice mixed rhythmic feel. Listen to the contrast between the loping, triplet feel on the drums vs. the punctuation of the piano... the same thing that gives the African piece above its exquisite swing.
How exactly would you count that? I don't know. Why bother? Either you can feel it and play it or you can't.
Now contrast that with the rhythmic environment in a version of the same song by one of today's best and most popular blues acts:
It's not bad, but do you hear the difference? The entire band sort of goes lump-de-lump-de-lump. The fecundity of the rhythmic milieu is much reduced.
But I digress beyond the scope of your question. I'd say 4/4 with a triplet feel is the easiest way to count time in the blues. Especially these days.