Is it completely unreasonable to try to drive I-5 from Orange County (Mission Viejo) up to LA (meeting friends in Thai Town for dinner) on a weeknight? I'm there for work and am off at 4:30, though could leave a bit earlier if it made a difference. Or is it better to leave much later (7)?

5 can be a mess at any time, but afternoon isn't anywhere near as consistently-a-parking-lot as morning. I wouldn't sweat over a decision between 4:30 or 7, you could choose one of them over the other and then run into two accidents along the way, so go with whatever time works best for you and cross your fingers.
You could also consider metrolink/amtrak if your friends can pick you up at Union Station.

I live where you are going to be - and I have driven to LA at 4:30 - it stinks but it is what it is. It will most likely bottle neck at certain points - just do it - you will meet them for dinner no issues just know that there will be traffic. I waiting a few weeks ago - and left at 7:00 to avoid traffic and exactly what joe said happened- there was an accident!

Thanks! How much time would you allow?

if you take the 405 and have 2 people the HOV lane rocks and moves pretty good.

It's a 50 mile trip and you'll be lucky if traffic averages 40mph at 4:30pm. So I'd say plan on being there around 6pm.

yes, 6-6:30

Thanks guys. Very helpful.