Connie, I've driven from Siena to Assisi. It's further than you think. But it's doable, that's for sure. Coming from Florence there are more Autostrada options than from Siena, which saves an INSANE amount of time in Tuscany (like three times!).
Assisi isn't very large. The cathedral and the tower at the top of the hill are about all there is to see. I doubled the day up with a few other Tuscan hill towns and it worked out perfectly. Just remember to multiply your driving time by about 3 if you're not on the Autostrada or other freeway-type highway.