I will be working in Madrid for a week with my meeting ending on Friday. I think the latest I will be able to stay in Spain is until Monday, so I was thinking that perhaps I could take the AVE on Friday night and return Sunday night? Is this a reasonable side trip?

Yes of course, being but 2 hours each way and Seville is a wonderful old town - yet in two days it's fairly compact and it will be a great weekend - especially Sat night when you hit the Flamenco parlours across the river.

Definitely - I went to Seville for a couple of nights as a side trip from a sun holiday in the Algarve and thought it was magical.

Friday night will be a great time to arrive, eveyone eats late in the tapas bars and you can go on a tapas crawl eating the finest food in the world (OK I'm getting carried away but you just can't beat the Seville tapas, my favourite is bocas rusas, red crab... fab...)

I would do it!
It is going to cost you , but it is worth it.

Yes, I would do it and try bto stay as centrally as you can afford.

IMO the two biggest attractions besides the architecture are the cathedral and the Alcazar and they are basically within easy walking distance of each other.