Say FDR dies of his polio infection sometime in the early 20's; his wife (as OTL) establishes herself as a real political figure in the NY Democratic Party during his illness, so when Al Smith needs it most in his re-election in 1924, Eleanor campaigns and makes a very important speech on his behalf.
This only increases her influence with the party, so that in 1928 she is able to secure her party's nomination for Governor, and wins a tough campaign in the general. When the Depression hits, she heads a very aggressive reaction by the state government (as her husband did OTL).
How plausible is all this?