Penarol is a huge favorites here. In first round they lost on one tough away game against LDU Quito, so here they are in must win situation. For sure with Flamengo they will try to reach the knockout stage. Their main opponent for that will be LDU, but it is too early about that. Here, they must win and I strongly believe in them. They will be without: Gargano and Pereira.
San Jose will be tough at home, but in away games I don't expect very good performance from them. In this competition from 92, they have 0-2-17 on the road and mostly of the defeats are with 2 or more goals difference. Also, in the local league they are not playing so well. The defense is weak, so, I doubt that they will be able to stop the home team here.
Simply, Penarol is a better team, home ground is a big advantage in this competition and all except one easy win for the hosts will be a surprise for me. Good luck !