1: skill tree progression is not shared between classes meaning for each class you can start the grind all over again.
1.2: most skill in said tree do not feel significant or unique

2: the basic blood skill (ultimates) multiplies your damage by x4 and gives you infinite ammo. the keystone ability of each class replaces this with something more niche and less usable
2.2: weapons utilizing the amount of shots you have fired before reloading are broken for the duration of the blood skill.

3: traits giving weapons multiple projectiles are on a cooldown and have a duration meaning your dps can fall right under you.

4: bosses are made to be awful to fight. most are programmed to either rush you down or to stay at a distance and cause some effect that forces you to after them. this means that if your wave management is sub par the bosses basically can't be dealt with ending your run.
4.2 one of the boss effects is permanent
4.3 the bosses and weapons are not designed with eachother in mind meaning that close range setups are unable to deal with certain bosses.

5 you autoshoot by default when aiming at enemies and a fair amount of weapons have strong dropoff. good luck aiming at fliers.